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Olli Kurkela,1– 3 Jorma Lahtela,4 Martti Arffman,1,2 Leena Forma1,3 1Faculty of Social Sciences, Tampere University, Tampere, 30014, Finland; 2Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL), Helsinki, 00271, Finland; 3Laurea University of Applied Sciences, Vantaa, 01300, Finland; 4Tampere University Hospital, Tampere, 33520, FinlandCorrespondence: Olli Kurkela, Health Sciences, Faculty of Social Sciences, Tampere University, P.O. Box 100, Tampere, 33014, Finland, Tel +358 50 5099170, Email olli.kurkela@tuni.fiAim: Infrared thermography (IRT) is a non-invasive technology for screening and early detection of diabetic foot. Real-world data and the Delphi technique were used to assess IRT’s potential effect on typical care pathways of diabetic foot and their costs in the Finnish healthcare setting.Methods: The most typical care pathways of diabetic foot were identified from national healthcare registers from 2011 to 2017. The effect of IRT in terms of avoidable care episodes was assessed by a Delphi panel including Finnish diabetic foot specialists (n=13). By combining a series of decision-analytic models, the IRT’s potential effect on the costs of each pathway and their sensitivity to model assumptions were estimated.Results: Hypothetical annual savings were estimated to be EUR ~1.7 million (EUR ~1.3 million–EUR ~2.5 million), constituting approximately 20% of the total annual care pathway costs examined. In the longer and more complex pathways, the application of IRT was estimated to result in notable savings while in the shorter pathways, IRT could increase costs.Conclusion: Our modeling suggests that IRT could potentially reduce costs in a Finnish healthcare setting. Given our analysis, generation of robust evidence on the effectiveness of recent IRT technologies with up-to-date protocols seems appropriate.Keywords: foot complication, infrared thermography, healthcare costs, cost analysis, expert panel, diabetic foot

Background: Perioperative dysglycaemias are a risk for harm but guidelines to improve glucose management are poorly adhered to. Aim: To determine whether a specialized team and diabetes education improves the implementation of guidelines and glucose values. Methods: We conducted a prospective study of 611 nonselected, consecutive patients attending for elective hip or knee arthroplasty. The first 209 patients received conventional care and the following 402 patients received intervention (Acute Glucose Service, AGS) in two chronological groups; either perioperatively (AGS1) or also preoperatively (AGS2). The AGS-team provided diabetes education, identified the patients with diabetes risk and adjusted the medication when needed. Capillary plasma glucose (CPG) was repeatedly measured and glycated haemoglobin (HbA1c) obtained before and after the surgery. The study objectives were to evaluate the staff actions when hyperglycaemia was severe (CPG >10 mmol/L), and to assess improvement of the glycaemic values and the complication rate within 3 months. Results: None of the severely hyperglycaemic events in the reference group were treated according to guidelines. In the AGS 1 group, 50% and in the AGS2 group, 53% were appropriately managed (p 7.8 mmol/L at least twice) and of severe hyperglycaemia (CPG >10 mmol/L) decreased in all patient groups. The medians of the highest, mean and variability of CPG values improved. The mean HbA1c improved significantly within AGS 2. There was no association between improved glycaemic care and early complications. Conclusions: AGS intervention significantly improves adherence to guidelines and glucose values. acceptedVersion

Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty.Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery. Actions of the attending teams to CPG values and detection of patients at risk were analysed.A total of 209 patients were enrolled. All diabetic patients on insulin (6/6) had hyperglycaemia (≥7.8 mmol/l) more than twice and severe hyperglycaemia (10 mmol/l) at least once. Of the 27 diabetic patients not on insulin 26 (96.3%) had CPG ≥ 7.8 mmol/l ≥ 2 times and 17 (63%)10 mmol/l. The corresponding figures of the 176 non-diabetic patients were 137 (77.8%) and 61 (34.7%). Severe hyperglycaemia occurred in 54/176 (30.1%) of the non-diabetic patients with pre-operative HbA1c 42 mmol/mol and random plasma glucose 7.8 mmol/l. Of the 84 hyperglycaemic episodes 10 mmol/l, none was treated. Patients with a FINDRISC score ≥ 12 (corresponding to moderate to high risk of diabetes) and hyperglycaemia went unnoticed.Hyperglycaemia is common among elective orthopaedic surgery patients with or without diabetes. More than 80% of the 209 patients had hyperglycaemia and 40% had severe hyperglycaemia. None of the patients was treated according to guidelines and none of the patients at risk of hyperglycaemia or diabetes was noticed. There is an obvious need for further education and support by diabetes specialists.Clinical trials, gov. NCT03306810.

Background: Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs. Methods: The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009. Use of medication was attained from the nationwide prescription database of the Social Insurance Institution of Finland. Median follow-up was 9.2 years postdiagnosis. A total of 1,603 (24,5%) men had used antidiabetic medication. A total of 771 men died of prostate cancer during the follow-up. We used multivariable-adjusted Cox regression to evaluate the risk of prostate cancer death and onset of androgen deprivation therapy (ADT) with adjustment for prostate cancer clinical characteristics, comorbidities and use of other drugs. Separate analyses were further adjusted for blood glucose. Results: Risk of prostate cancer death was higher among antidiabetic drug users overall (HR = 1.42; 95% CI, 1.18–1.70) compared with nonusers, separately among insulin and metformin users. Adjustment for blood glucose level abolished the risk increase. Risk of ADT initiation was increased among the medication users (HR = 1.26; 95% CI, 1.05–1.49). Conclusions: Men with prostate cancer using antidiabetic medication are generally at increased risk of dying from prostate cancer compared with nonusers. The risk association is driven by underlying diabetes, as adjustment for blood glucose level ameliorates the risk increase. Impact: Type 2 diabetes should be considered as a risk factor when considering prostate cancer prognosis.

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

Background Data on the prevalence of pancreatic dysfunction after an episode of acute pancreatitis are conflicting. Our aim was to evaluate the natural course of endocrine and exocrine pancreatic function in the long-term follow-up after the first episode of acute alcoholic pancreatitis (AAP). Methods A total of 77 patients who survived their first episode of AAP between January 2001 and February 2005 were prospectively followed up for a maximum of 13 years. During the follow-up, patients were repeatedly interviewed and monitored for recurrences, new diabetes, and chronic pancreatitis. The pancreatic function was evaluated repeatedly during the follow-up. Results Of the patients, 35% had ≥1 recurrent acute pancreatitis (RAP) episodes during the follow-up. New pancreatogenic diabetes developed in 19% of the previously nondiabetic patients, but only in patients with RAP (13/26 vs. 0/42; OR=39; 95% CI, 4.6-327.1). In addition, 55% of the patients developed new prediabetes or diabetes, and even this was more frequent in patients with RAP (86% vs. 42%; OR=8.2; 95% CI, 1.2-54.3). Exocrine dysfunction developed in 24% of the patients and was associated with abnormal findings in the endocrine function (P=0.003). Patients with RAP had a higher overall mortality compared with patients without RAP episodes during the follow-up (36% vs. 13%; HR=4.0; 95% CI, 1.4-11.0). Conclusions The risk for pancreatic endocrine dysfunction, pancreatogenic diabetes and mortality increases significantly if the patient has recurrent episodes of AAP. The risk of developing pancreatic dysfunction after AAP should be recognized and pancreatic function should be screened routinely during the years after the first episode of AAP.

Background: Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial. Methods: Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N = 442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms. Results: Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95% CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (k = 0.88) in the SA and 95.4% (k = 0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06). Conclusions: A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling. (C) 2016 Elsevier Ltd. All rights reserved.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Aims: The understanding of second-line use of glucose-lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Our aim was to describe second-line GLD treatment patterns in four Nordic countries.Methods: All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries. Second-line treatment was defined as a prescription of a second GLD class following ≥6 months of metformin monotherapy. Index was the date of first dispense of the second-line drug.Results: A rapid uptake of newer GLDs (GLP-1RA, DPP-4i and SGLT-2i) over the 10-year observation period was seen in Denmark, Finland and Norway, while slower in Sweden. In 2015, 33,880 (3.1%) of 1,078,692 T2D patients initiated second-line treatment, and newer GLDs were more commonly used in Finland (92%), Norway (71%) and Denmark (70%) vs Sweden (44%). In 2015, the use of older GLDs (insulin and sulphonylureas) was 7-fold greater in Sweden compared to Finland (49% vs 7%), and 1.6-fold greater compared with Denmark and Norway (49% vs 30% and 29%, respectively).Conclusions: Despite comparable demography and healthcare systems in four neighbouring countries, surprisingly large differences in second-line use of newer GLDs were found. With recent evidence of potential cardiovascular benefits with newer GLDs, such differences may have an important impact on cardiovascular outcomes.

BACKGROUND: Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS: Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS: In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS: Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.

Doel Onderzoek naar het voorkomen en de impact van niet-ernstige hypoglycemieen bij mensen met type 1 diabetes (T1D) en met insuline behandelde type 2 diabetes (T2D) in Nederland. Deze studie is onderdeel van de internationale HIT-studie die is uitgevoerd in zeven Europese landen.

Hypoglycemia is a frequent side effect induced by insulin treatment of type 1 (T1DM) and type 2 diabetes (T2DM). Limited data exist on the associated healthcare resource use and patient impact of hypoglycemia, particularly at a country-specific level. This study investigated the effects of self-reported non-severe hypoglycemic events (NSHE) on use of healthcare resources and patient wellbeing.Patients with T1DM or insulin-treated T2DM diabetes from seven European countries were invited to complete four weekly questionnaires. Data were collected on patient demographics, NSHE occurrence in the last 7 days, hypoglycemia-related resource use, and patient impact. NSHE were defined as events with hypoglycemia symptoms, with or without blood glucose measurement, or low blood glucose measurement without symptoms, which the patient could manage without third-party assistance.Three thousand, nine hundred and fifty-nine respondents completed at least one wave of the survey, with 57% completing all four questionnaires; 3827 respondents were used for data analyses. Overall, 2.3% and 8.9% of NSHE in patients with T1DM and T2DM, respectively, resulted in healthcare professional contact. Across countries, there was a mean increase in blood glucose test use of 3.0 tests in the week following a NSHE. Among respondents who were employed (48%), loss of work-time after the last hypoglycemic event was reported for 9.7% of NSHE. Overall, 10.2% (daytime) and 8.0% (nocturnal) NSHE led to work-time loss, with a mean loss of 84.3 (daytime) and 169.6 (nocturnal) minutes among patients reporting work-time loss. Additionally, patients reported feeling tired, irritable, and having negative feelings following hypoglycemia.Direct comparisons between studies must be interpreted with caution because of different definitions of hypoglycemia severity, duration of the studies, and methods of data collection.NSHE were associated with use of extra healthcare resources and work-time loss in all countries studied, suggesting that NSHE have considerable impact on patients/society.

Aims Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self-reported non-severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin-treated Type 2 diabetes mellitus. Methods People in seven European countries aged >15 years with Type 1 diabetes or insulin–treated Type 2 diabetes (basal-only, basal-bolus and other insulin regimens) were recruited via consumer panels, nurses, telephone recruitment and family referrals. Respondents completed four online questionnaires. The first questionnaire collected background information on demographics and hypoglycaemia-related behaviour, whilst all four questionnaires collected data on non-severe hypoglycaemic events in the preceding 7 days. Results Analysis was based on 11 440 respondent-weeks from 3827 respondents. All participants completed the first questionnaire and 57% completed all four. The mean number of events/respondent–week was 1.8 (Type 1 diabetes) and 0.4–0.7 (Type 2 diabetes, with different insulin treatments) corresponding to annual event rates of 94 and 21–36, respectively. A total of 63% of respondents with Type 1 diabetes and 49–64% of respondents with Type 2 diabetes, treated with different insulin regimens, who experienced hypoglycaemic events, reported impaired hypoglycaemia awareness or unawareness. A high proportion of respondents rarely or never informed their general practitioner/specialist about hypoglycaemia: 65% (Type 1 diabetes) and 50–59% (Type 2 diabetes). Overall, 16% of respondents with Type 1 diabetes and 26% of respondents with Type 2 diabetes reported not being asked about hypoglycaemia during routine appointments. Conclusion Non-severe hypoglycaemic events are common amongst people with Type 1 diabetes and insulin–treated Type 2 diabetes in real-world settings. Many rarely or never inform their general practitioner/specialist about their hypoglycaemia and the real burden of hypoglycaemia may be underestimated.

In this study, we evaluated the effects of the re-organization of inpatient care for patients with a diabetic foot infection, and the implementation of a specialized multi-disciplinary wound department at an academic tertiary hospital.This was a retrospective cohort study, comprising 272 patients treated for diabetic foot infections in 2006-2007 (Group 1, n=124) and 2013-2014 (Group 2, n=148). In 2012, inpatient care of all chronic wounds was centralized at a single wound department with a multi-disciplinary team. We assessed group outcome before and after the re-organization.During the 7-year study period, the incidence of hospitalized patients with a diabetic foot infection increased 19%. After initiating the re-organization, the below-the-knee amputation rate was significantly reduced (25.8% vs. 9.5%, p0.001). The median time from admission to surgical intervention decreased from 5days to 2days, p0.001. The length of hospitalization also tended to decrease after the reorganization.The findings of this study demonstrate the benefits of treating diabetic foot infections at a specialized wound department with a multi-disciplinary team. The benefits were achieved by simply distributing the workload and organizing schedules, without new investments or additional personnel. The findings of this study indicate that patients with diabetic foot infections present a challenge that is beyond the expertise of a single field of medicine. A working collaboration between disciplines and a specialized wound department are central in achieving better results.

Aims:Although obesity is a risk factor for coronary heart disease (CHD), it might be associated with a favourable prognosis in patients with CHD. The aim of the study was to evaluate this so called ‘obesity paradox’ during a follow-up period of 20 years in patients who had undergone coronary artery bypass grafting (CABG).Methods and results:The study population consisted of 922 CHD patients who had undergone CABG between 1993 and 1994. Pre and perioperative data was collected from patient records and supplemented with patient questionnaires, telephone contacts and data from national archives. The 10-year postoperative prognosis of normal-weight patients (body mass index (BMI) 18.5–24.9 kg/m2) was inferior to that of overweight (BMI 25.0–29.9 kg/m2) and obese patients (BMI⩾30.0 kg/m2) and to the background population. Beyond 10 years the prognosis of obese patients deteriorated when compared with the overweight group. At the end of the 20-year follow-up, survival of the normal weight group was 0.68 (95% co...

To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head-up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol.Thirty-three healthy volunteers (21-51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole-body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head-up tilt, and repeated during the same session and on four separate days.During the head-up tilt, diastolic BP (5.2+/-0.6%), heart rate (27.6+/-1.9%) and vascular resistance (12.5+/-1.7%) increased (all p0.05), while systolic BP (-3.2+/-0.6%), aortic pulse pressure (-23.3+/-1.4%), augmentation index (-11.6+/-0.7%), aortic reflection time (-7.0+/-1.0%), ejection duration (-21.4+/-0.7%), stroke volume (-26.1+/-1.2%) and cardiac output (-5.0+/-1.5%) decreased (all p0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = -0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head-up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = -0.445). According to Bland-Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days.Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head-up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

Statins are cholesterol-lowering drugs that are widely used to prevent and treat atherosclerotic cardiovascular disease. Recent research from both in vitro and in vivo studies suggests that there is an association between the use of statins and a reduction in the incidence of and mortality from prostate cancer. Several mechanisms of action that might bring about these beneficial effects of statins have been proposed, most of which include direct effects of statins on intracellular signaling. In this Review we discuss the current knowledge on the use of statins to prevent prostate cancer. We will also look at future directions for clinical research on this topic.

Accurate assessment of the causes of death is crucial for a conclusive evaluation of the ongoing prostate cancer screening trials. Here, we report the validity of the official causes of death as compared with an independent expert review in the Finnish prostate cancer screening trial. Because nearly 80,000 men were involved, death-cause evaluation was restricted to men diagnosed for prostate cancer. Medical charts were retrieved and the cause of death was assigned by an expert review panel for all deaths among men with prostate cancer during the study period, 1996-2003. The panel decision was compared with both death certificates and the official causes of death as assigned by Statistics Finland. Of a total of 315 deaths, the review panel attributed 127 (41%) to prostate cancer and 184 (59%) to other causes, the corresponding figures in death certificates being 124 (40%) and 187 (60%). Four cases were excluded because of insufficient information. The death-certificate data were in agreement with the panel's assessment in 305 out of 311 cases (overall agreement 97.7%, kappa = 0.95). The overall agreement between the official causes of death and the panel's decision was 97.4% (304/311, kappa = 0.95). The sensitivity of the certificates in identifying prostate cancer deaths was 96.1% (panel as golden standard). Correspondingly, specificity was 98.9%. The official causes of death thus provide an accurate means for evaluating disease-specific mortality in a large population-based prostate-cancer screening trial in Finland.

In the present article, we review current knowledge of the epidemiology, diagnosis, and treatment of peripheral vascular disease in patients with end-stage renal disease. The main focus is placed on diabetic patients receiving peritoneal dialysis, but studies on patients receiving hemodialysis are also reviewed, because most reports involve this patient group, and the number of reports on peripheral vascular disease in PD patients alone is limited.

OBJECTIVE—To assess the prevalence of the metabolic syndrome (MetS) in two independent Finnish study cohorts. RESEARCH DESIGN AND METHODS—The prevalence of the MetS by modified World Health Organization criteria was analyzed in different categories of glucose tolerance in a cross-sectional, population-based sample of 2,049 individuals (FINRISK) aged 45–64 years and in 522 participants of the Finnish Diabetes Prevention Study (DPS) with impaired glucose tolerance (IGT). RESULTS—In the FINRISK cohort, the MetS was present in 38.8% of the men and 22.2% of the women. The prevalence was 14.4 and 10.1% in subjects with normal glucose tolerance, 74.0 and 52.2% in subjects with impaired fasting glucose, 84.8 and 65.4% in subjects with IGT, and 91.5 and 82.7% in subjects with type 2 diabetes in men and women, respectively. Among women, the prevalence of the MetS increased with increasing age. In the DPS cohort, the MetS was present in 78.4% of the men and 72.2% of the women with IGT. CONCLUSIONS—The MetS was extremely common in middle-aged subjects The high prevalence in men was mostly due to their high waist-to-hip ratio. The prevalence of the MetS increased in both sexes with deterioration in glucose regulation. Approximately 75% of the subjects with IGT had the MetS. Because the syndrome includes the major risk factors for atherosclerotic vascular diseases and is the major antecedent for type 2 diabetes, concerted preventive action should be targeted to control all the features of the MetS.

Background and Aims:The incidence of diabetic Charcot neuroarthropathy has increased. The purpose here was to study the current diagnostics and treatment of the Charcot foot.Materials and Methods:During a time period from 1994 to 2000, a total of 36 feet were diagnosed as cases of diabetic Charcot neuroarthropathies. A retrospective analysis of patient records and radiographs was undertaken. A review of the recent literature is presented.Results:29 cases were diagnosed in the dissolution stage, 2 in coalascence, and 5 in the resolution stage. The diagnostic delay averaged 29 weeks. Treatment with cast immobilisation ranged from 4 to 37 weeks (mean 11 weeks). A total of 14 surgical procedures were carried out on 10 patients: six exostectomies, four midfoot arthrodeses, one triple arthrodesis, one tibiocalcaneal arthrodesis and two below-knee amputations. radiological fusion was achieved in two thirds of the attempted arthrodeses.Conclusions:A physician should always consider the Charcot neuroarthropathy when a diabetic patient has an inflamed foot. In the absence of fever, elevated CRP or ESR, infection is a highly unlikely diagnosis, and a Charcot process should primarily be considered. The initial treatment of an inflamed Charcot foot consists in sufficiently long non-weightbearing with a cast, which should start immediately after the diagnosis. The prerequisites of successful reconstructive surgery are correct timing, adequate fixation and a long postoperative non-weightbearing period. In the resolution stage most Charcot foot patients need custom-molded footwear.

OBJECTIVE To investigate the clinical efficacy of zoledronic acid in patients with diabetes and acute Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS Thirty-nine consecutive patients were randomly assigned to placebo or three intravenous infusions of 4 mg zoledronic acid. The primary outcome was clinical resolution of acute Charcot neuroarthropathy determined by total immobilization time (casting plus orthosis). RESULTS At baseline, there was no significant difference between the randomly assigned groups with respect to Charcot disease activity or other baseline values. In the zoledronic acid group, the median time for total immobilization was 27 weeks (range 10–62), and in the placebo group it was 20 weeks (20–52) (P = 0.02). CONCLUSIONS Zoledronic acid had no beneficial effect on the clinical resolution of acute Charcot neuroarthropathy in terms of total immobilization time. It is possible that it may prolong the time to clinical resolution of Charcot neuroarthropathy.

Objective To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). Design Cross-sectional study. Setting Tertiary-care university hospital. Patients We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34 – 70 years), duration of diabetes was 27.5 years (range: 17 – 39 years), and duration of CAPD was 16.5 months (range: 2 – 59 months). Outcome Measures Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. Results Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR ( r = –0.82, p < 0.05). The area of the lesions correlated directly with body weight ( r = 0.80, p < 0.05) and inversely with weekly Kt/V urea ( r = –0.90, p < 0.01). Conclusions Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high.

Background: The purpose of surgical closure of atrial septal defect (ASD) is to relieve the cardiovascular system from a haemodynamic burden. Excessive amounts of atrial peptides are released in congestive heart failure, valvular diseases and congenital heart diseases. Aims: To examine whether patients after surgical repair of ASD have higher concentrations of N-terminal atrial natriuretic peptide (ANP-N) than age-, sex- and body mass index (BMI)-matched control subjects. Methods: Medical history, physical examination, standard 12-lead electrocardiogram, and ANP-N concentrations were obtained in 65 adult patients operated for ASD at the age of 21 ± 13 years (mean ± standard deviation), 21 ± 6 years after surgical closure of ASD. Sixty-seven healthy subjects matched for age, sex and BMI served as controls. Results: In the patients serum ANP-N was higher than in the control subjects 0.41 ± 0.32 nmol/l, median 0.31 nmol/l, interquartile range (IQR) 0.21–0.49 nmol/l vs. 0.24 ± 0.12 nmol/l, median 0.23 nmol/l, IQR 0.17–0.29 nmol/l, (P = 0.0003). Patients with concomitant diseases had higher ANP-N concentrations (0.51 ± 0.39 nmol/l, median 0.34, IQR 0.26–0.73 nmol/l) than ASD patients without any history or signs of disease (0.28 ± 0.16 nmol/l, median 0.27, IQR 0.17–0.40 nmol/l, P = 0.01). The ‘healthy’ ASD patients had higher hormone concentrations than age-, sex- and BMI-matched control subjects (0.28 ± 0.16 median 0.27 nmol/l, IQR 0.17–0.40 nmol/l and 0.21 ± 0.07 nmol/l, median 0.20 nmol/l, IQR 0.15–0.27 nmol/l, P = 0.01). Multiple stepwise linear regression analysis showed that age at operation was strongly associated with the post-operative ANP-N concentration (r2 = 0.25, P = 0.0002). Conclusion: ASD patients have higher ANP-N concentrations late after surgical repair. Hormone levels correlate with age at operation. Our finding supports the clinical praxis of operating on these patients in their childhood and adolescence.

ObjectiveTo determine the effects of subcutaneous (SC) and intraperitoneal (IP) insulin on serum leptin concentration in type I diabetic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD).DesignProspective, open, before–after study.SettingTertiary-care university hospital.ParticipantsTwelve type I diabetic patients with stabilized CAPD, age 43.9 ± 2.8 years, and duration of diabetes 30.4 ± 3.5 years.InterventionAfter stabilized CAPD therapy, all patients were treated first with SC insulin for a median of 3 months, and thereafter with IP insulin for another 3 months.Main Outcome MeasuresPlasma leptin, insulin sensitivity with euglycemic clamp, and glycemic and uremic status after both treatment periods.ResultsDuring SC insulin therapy, plasma leptin concentration was significantly higher than during IP insulin (19.8 ± 5.9 ng/mL and 12.8 ± 6.2 ng/mL, respectively; p < 0.001). Leptin concentration was higher in CAPD patients and was related to body mass index in both genders. No correlation was detected between plasma leptin and fasting insulin, glycemic control, glucose disposal rate, or serum lipids.ConclusionPlasma leptin concentration is lower during IP insulin therapy compared to SC insulin. Insulin has probably a direct effect on both peritoneal leptin clearance and adipose tissue leptin production. The significance of leptin in regulating appetite and anorexia in uremia remains unclear.

Objective To evaluate the influence of subcutaneous and intraperitoneal (IP) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). Design A before–after trial. Setting University hospital outpatient care. Participants Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 ± 2.9 (SEM) years and duration of diabetes 31.4 ± 3.4 years. Intervention Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with IP insulin. The studies were performed after a median time of 3 months on each treatment. Main Outcome Measures Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. Results After changing from subcutaneous insulin to IP insulin, plasma HDL cholesterol decreased (from 1.29 ± 0.13 mmol/L to 0.96 ± 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased ( p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 ( p < 0.01). ApoA-I ( p < 0.05) decreased while the ApoB/ApoA-I ratio ( p < 0.01) and the ApoA-I/HDL-cholesterol ratio ( p < 0.01) increased during IP insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin ( p < 0.01). Conclusions In diabetic patients on CAPD therapy, IP insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A^ 10.00±0.38% after subcutaneous and 8.40±0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28±0.18 mmol/L vs 0.88±0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect on serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.

1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a crossover manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-3H]glucose as a tracer. 2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% ± 0.46% and 9.52% ± 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy. 3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery. 4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.

Hyponatremia due to psychoactive drugs commonly used in the treatment of elderly patients appears usually during the first weeks of treatment. Blood sodium level should be measured before the initiation of medication and checked after a few weeks. Symptoms suggesting hyponatremia in a patient under psychoactive medication are always an indication for checking the sodium level. Restriction of fluid intake to one and a half liters per day may correct mild hyponatremia. First-line treatment is always cessation of drug therapy. If the psychoactive drug is essential for the patient's disease, it will be changed to a different one.

Purpose: To describe a specific imaging pattern of hepatic fatty change typical of diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) treated with intraperitoneal (i.p.) insulin. Material and Methods: Liver ultrasound was applied in 16 CAPD patients with insulin-dependent diabetes mellitus. Presence of hepatic subcapsular steatosis and maximum thickness of the fatty layer were recorded. Liver MR examination was made of 1 patient found to have extensive subcapsular steatosis. Results: Hepatic ultrasound revealed a typical pattern of subcapsular steatosis ("coating-of-fat") in 7/8 patients treated with i.p. insulin. None (0/8) of the diabetic CAPD patients treated with subcutaneous insulin had subcapsular steatosis. Conclusion: Hepatic subcapsular steatosis is specific to CAPD patients on i.p. insulin treatment. To our knowledge this is the first report to describe imaging findings in this particular form of hepatic fatty change.

Background There is only sparse scientific data about the long-term effects of the Charcot foot on patients' lives and the clinical outcome. This study evaluates the long-term effects of diabetic Charcot foot. Methods A cross-sectional follow-up study of consecutive series of patients with Charcot foot referred to the University Hospital Diabetic Foot and Ankle Clinic between 1991 and 2002. Results Forty-one patients were referred with Charcot foot between 1991 and 2002. After an average follow-up of 8 years their overall mortality rate was 29% (12/41) and 29 patients (30 Charcot feet) have been followed more than 5 years. Sixty-seven percent of Charcot feet suffered at least one episode of ulceration and 50% (15/30) of affected feet had surgical treatment resulting in 29 operations. Simple exostectomy was successful in 62% of cases. The need for surgical management increased markedly 4 years after the diagnosis. Correct diagnosis within 3 months resulted in better functional outcome (AOFAS) and walking distance ( p =0.006 and p =0.008, respectively). Lower SF-36 component scores in physical functioning, social functioning and general health perceptions were found when the study population was compared to the general population and chronically ill control subjects. Conclusions Diabetic Charcot foot decreases patient's physical functioning and general health but does not usually affect mental health. Surgical management is often required with an increase 4 years post-diagnosis. A delay of diagnosis of more than 3 months was found to adversely affect the quality of life and functional outcome.

Decreased risk of prostate cancer in diabetic men has been reported. The authors evaluated the association between antidiabetic medication use and prostate cancer at the population level. All incident prostate cancer cases in Finland during 1995-2002 were identified from the Finnish Cancer Registry. Matched controls were provided by the Population Register Center (24,723 case-control pairs). Information on medication use was obtained from a comprehensive prescription database. Multivariable-adjusted odds ratios were computed by using conditional logistic regression. The authors found that prostate cancer risk was decreased for antidiabetic medication users (odds ratio = 0.87, 95% confidence interval: 0.82, 0.92). The decrease was observed for most drug groups. The odds ratio decreased in a dose-dependent fashion by quantity of use. Duration of antidiabetic treatment was inversely associated with overall prostate cancer risk and risk of advanced cancer. Similar risk reduction for users of different antidiabetic drugs suggests that diabetes, instead of the medication itself, is behind the association. This finding is unlikely to be secondary because of differential uptake of the prostate-specific antigen test or different prostate-specific antigen levels between medication users and nonusers; prevalence of testing in Finland is low. Dose and time dependency of the relation probably indicates that duration of diabetes is negatively associated with risk.

OBJECTIVE—The aim of this secondary analysis of the Finnish Diabetes Prevention Study was to assess the effects of lifestyle intervention on metabolic syndrome and its components. RESEARCH DESIGN AND METHODS—A total of 522 middle-aged overweight men and women with impaired glucose tolerance were randomized into an individualized lifestyle intervention group or a standard care control group. National Cholesterol Education Program criteria were used for the definition of metabolic syndrome. RESULTS—At the end of the study, with a mean follow-up of 3.9 years, we found a significant reduction in the prevalence of metabolic syndrome in the intervention group compared with the control group (odds ratio [OR] 0.62 [95% CI 0.40–0.95]) and in the prevalence of abdominal obesity (0.48 [0.28–0.81]). CONCLUSIONS—The results suggest that lifestyle intervention may also reduce risk of cardiovascular disease in the long run.

Background: Previous studies have shown that statin use may reduce prostate cancer risk. In the current study, we evaluated the association between serum cholesterol–lowering medication use and prostate cancer risk at the population level. Materials and Methods: All newly diagnosed prostate cancer cases in Finland during 1995 to 2002 and matched controls (24,723 case control pairs) were identified from the Finnish Cancer Registry and the Population Register Center, respectively. Detailed information on cholesterol-lowering drug purchases during the study period was obtained from the prescription database of the Social Insurance Institution of Finland. Results: After adjustment for potential confounders, having ever-use of any statin was associated with marginally elevated overall prostate cancer risk [odds ratio (OR), 1.07; 95% confidence interval (95% CI), 1.00-1.16]. However, none of the statins was associated with the overall prostate cancer risk when analyzed separately. On the other hand, the risk of advanced prostate cancer was decreased among users of atorvastatin, lovastatin, and simvastatin (OR 0.61, 95% CI 0.37-0.98; OR 0.61, 95% CI 0.43-0.85; and OR 0.78, 95% CI 0.61-1.01, respectively). The risk was not affected among users of other cholesterol drug groups. Conclusions: Our large population-based study showed no evidence for reduced overall prostate cancer risk among users of cholesterol-lowering drugs, whereas the risk of advanced cancer was decreased among statin users. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2226–32)

Accurate assessment of the causes of death is crucial for a conclusive evaluation of the ongoing prostate cancer screening trials. Here, we report the validity of the official causes of death as compared with an independent expert review in the Finnish prostate cancer screening trial. Because nearly 80,000 men were involved, death-cause evaluation was restricted to men diagnosed for prostate cancer. Medical charts were retrieved and the cause of death was assigned by an expert review panel for all deaths among men with prostate cancer during the study period, 1996-2003. The panel decision was compared with both death certificates and the official causes of death as assigned by Statistics Finland. Of a total of 315 deaths, the review panel attributed 127 (41%) to prostate cancer and 184 (59%) to other causes, the corresponding figures in death certificates being 124 (40%) and 187 (60%). Four cases were excluded because of insufficient information. The death-certificate data were in agreement with the panel's assessment in 305 out of 311 cases (overall agreement 97.7%, kappa = 0.95). The overall agreement between the official causes of death and the panel's decision was 97.4% (304/311, kappa = 0.95). The sensitivity of the certificates in identifying prostate cancer deaths was 96.1% (panel as golden standard). Correspondingly, specificity was 98.9%. The official causes of death thus provide an accurate means for evaluating disease-specific mortality in a large population-based prostate-cancer screening trial in Finland.

Aim: To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥ 6.5 and ≤10%] on metformin monotherapy. Methods: After a metformin dose titration/stabilization period (≥1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N = 584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA1c changes from baseline at Week 52 using a per-protocol approach. Results: From a mean baseline of 7.5%, HbA1c changes from baseline were −0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA1c < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were −0.56 mmol/l (−10.0 mg/dl) and −0.42 mmol/l (−7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline =−1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) =−2.5 kg (−3.1, −2.0); p < 0.001]. Conclusions: In this study, the addition of sitagliptin compared with glipizide provided similar HbA1c-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.

To assess the prevalence of the metabolic syndrome (MetS) in two independent Finnish study cohorts.The prevalence of the MetS by modified World Health Organization criteria was analyzed in different categories of glucose tolerance in a cross-sectional, population-based sample of 2,049 individuals (FINRISK) aged 45-64 years and in 522 participants of the Finnish Diabetes Prevention Study (DPS) with impaired glucose tolerance (IGT).In the FINRISK cohort, the MetS was present in 38.8% of the men and 22.2% of the women. The prevalence was 14.4 and 10.1% in subjects with normal glucose tolerance, 74.0 and 52.2% in subjects with impaired fasting glucose, 84.8 and 65.4% in subjects with IGT, and 91.5 and 82.7% in subjects with type 2 diabetes in men and women, respectively. Among women, the prevalence of the MetS increased with increasing age. In the DPS cohort, the MetS was present in 78.4% of the men and 72.2% of the women with IGT.The MetS was extremely common in middle-aged subjects The high prevalence in men was mostly due to their high waist-to-hip ratio. The prevalence of the MetS increased in both sexes with deterioration in glucose regulation. Approximately 75% of the subjects with IGT had the MetS. Because the syndrome includes the major risk factors for atherosclerotic vascular diseases and is the major antecedent for type 2 diabetes, concerted preventive action should be targeted to control all the features of the MetS.

This paper reviews telemedicine and its recent expansions within diabetes management. Diabetes mellitus continues to be one of the major chronic diseases with up to 11% of national health care expenditure, when all late complications are taken into account. Over and above this, the incidence of diabetes is increasing in pandemic fashion. Diabetes has been the focus of telemedicine and information technology over the past two decades. Useful applications supporting high quality treatment exist in clinical management, education, decision support and modelling. Development of high-speed networks enables transmission of good quality photographs making consultations from distant locations possible. Databases and data analysis are fundamental to diabetes outcome research. Less successful has been the development of electronic medical records although this is a dream of many. Evidence of improved clinical outcome using telemedical applications still awaits the breakthrough.

The associations of metabolic syndrome (MetS) or diabetes mellitus (DM) on long-term survival after coronary artery bypass grafting (CABG) have not been extensively evaluated. The aim of the present study was to assess the impact of MetS and DM on the 16-year survival after CABG. Methods Diabetic and metabolic status together with relevant cardiovascular data was established in 910 CABG patients operated in 1993-94. They were divided in three groups as follows: neither DM nor MetS (375 patients), MetS alone (279 patients) and DM with or without MetS (256 patients). The 16-year follow-up of patient survival was carried out using national health databases. The relative survival rates were analyzed using the Life Table method comparing the observed survival rates of three patient groups to the rates based on age-, sex- and time-specific life tables for the whole population in Finland. To study the independent significance of MetS and DM for clinical outcome, multivariate analysis was made using an optimizing stepwise procedure based on the Bayesian approach. Results Bayesian multivariate analysis revealed together six variables to predict clinical outcome (2 months to 16 years) in relation to the national background population, i.e. age, diabetes, left ventricular ejection fraction, BMI, perfusion time during the CABG and peripheral arterial disease. Our principal finding was that after postoperative period the 16-year prognosis of patients with neither DM nor MetS was better than that of the age-, sex-and time-matched background population (relative survival against background population 1.037, p < 0.0001). The overall survival of MetS patients resembled that of the matched background population (relative survival 0.998, NS). DM was associated with significantly increased mortality (relative survival 0.86, p < 0.0001). Additionally, mortality was even higher in patients receiving insulin treatment than in those without. Excess death rate of DM patients was predominantly caused by cardiovascular causes. Conclusion In this long-term follow-up study patient groups without diabetes had at least equal 16 years’ survival after CABG than their matched background populations. Survival of DM patients started to deteriorate already few years after the operation. BioMed Central open access

The effects of alcohol and aspirin on HbA1c chromatography in the Mono S method were studied in vitro and in vivo. A modified chromatography with enhanced resolution was used, making possible detailed examination of minor interfering peaks included in the routine HbA1c value. Incubation with acetylsalicylic acid increased a hemoglobin fraction separate from HbA1c. In vivo this fraction was elevated by 0.1% of the total hemoglobin during therapeutic aspirin ingestion for one month. In vitro acetaldehyde generated two labile hemoglobin fractions and slightly increased a minor stable fraction which was also elevated in vivo in both alcoholics and heavy drinkers. In relation to the HbA1c concentration, this stable fraction was equal in both alcoholic groups. We conclude that the in vivo effects of both aspirin and alcohol are negligible in routine HbA1c determination. Factors other than acetaldehyde might account for the unexpected HbA1c values in alcoholics.

To study the effect of uremia on hemoglobin A1c determination by the Mono S FPLC method, samples from uremic patients, with and without diabetes, and controls, were analysed with a modified chromatography with enhanced resolution. Besides specific HbA1c, four minor peaks could be seen, included in routine HbA1c values. Two of these differed in concentration in the patient groups studied: a shoulder-like peak close to the specific HbA1c (S fraction) and a slightly less cationic minor peak (M fraction). Both S and M peaks were higher in uremic than in nonuremic subjects, but the M peak was associated more with diabetes. In the nondiabetic group, the mean routine HbA1c value was 0.8% units higher in uremic than nonuremic individuals. The specific HbA1c was nondependent on uremia. Thus, in uremic patients, there seems to be falsely elevated HbA1c values, mainly because of small interfering hemoglobin fractions, not specific HbA1c.

OBJECTIVE To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro B29) in severe insulin resistance caused by human insulin antibodies. CASE: A 27-year-old man with a history of diabetes treated with human insulin for 3 years developed severe immunological insulin resistance caused by human insulin antibodies. Throughout follow-up (12 months) the insulin analog lispro was administered with an infusion pump as the only insulin therapy. The insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. CONCLUSIONS The insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased insulin antibody levels Apparently, the structural difference between the lispro and human insulin molecules prevented lispro from binding to the human insulin antibodies in this patient and consequently was nonimmunogenic.

BACKGROUND Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

OBJECTIVE To determine the occurrence of elevated fetal hemoglobin (HbF) among the diabetic population and determine the clinical situation of importance. RESEARCH DESIGN AND METHODS A cross-sectional study was conducted. HbA1c. and HbF were measured with high-performance liquid chromatogra-phy in 1,104 consecutive diabetic patients attending our clinic for HbA1c determination. The expression of clinical correlations between the high and low HbF group was performed for adults (≥15 years). A nondiabetic control group (n = 258) with the same age and sex distribution was included. RESULTS HbF was elevated (>1.0% of total hemoglobin) in 7.5% of the total diabetic group. In the adult diabetic group, HbF was elevated in 6.5% of the patients, and in the control group, HbF was elevated in 1.9% (P < 0.01). In the insulin-treated adult group, HbF was elevated in 10.2% of the patients, and in the non-insulin-treated group, HbF was elevated in 3.8%. The mean HbA1c was 8.90 ± 2.00% among the patients and 5.52 ± 0.53% in the control subjects (P < 0.001). Patients with elevated HbF were younger (P < 0.02) and more often on insulin therapy (P < 0.001) or type I diabetic patients (P < 0.001). Sex, glycemic control, or duration of diabetes were not significantly different in the patients with high or low HbF. Correlation was not detected between the amount of HbF and HbA1c or age in the group of patients with elevated HbF. Hemoglobinopathies, anemias, or malignancies were not diagnosed from the patients with high HbF. CONCLUSIONS Level of HbF is increased (>1.0%) among 7.5% of unselected diabetic patients. In adult (≥15 years) diabetic patients, it is increased among 6.5%, which is 3.4 times more often than in the control population. Acute hematological conditions or malignancies do not explain the difference. Elevated HbF seems to be associated with type I diabetes and insulin treatment.