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Hypoglycaemia is a feared complication of insulin-treated diabetes. Treatment recommendations vary worldwide and their implementation is poorly documented. The primary study objective was to assess adherence to broad guidelines of hypoglycaemic treatment; initially with quick-acting carbohydrate and follow up with long-acting carbohydrate. The secondary objective was to assess if initial treating carbohydrate quantity complied with current worldwide recommendations. Assessment was by questionnaire, which was validated, piloted and administered to all insulin-treated individuals attending routine outpatient diabetes clinic appointments over four weeks. The questionnaire response rate, readability and validity were acceptable at 74%, grade 6 level and 0.61 (Cohen's kappa), respectively. Assessment of broad guidelines for treatment of hypoglycaemia showed 78% of responders reported initial treatment with recommended foods, but only 40.8% of these were quick-acting carbohydrate. Only 55.8% reported ingesting follow-up food. Assessment of initial treating carbohydrate quantity showed 20.6% of responders used quantities exceeding all guidelines. Of the remaining, 46.4% used quantities consistent with the most liberal recommendations (European Association for the Study of Diabetes). Most study participants reported treating with recommended foods in quantities exceeding minimum recommendations, possibly attempting to resolve unpleasant symptoms of hypoglycaemia quickly. Failure of many to ingest follow-up food is concerning and warrants investigation. Increased patient education and standardisation of guidelines for treatment of hypoglycaemia are indicated. Copyright © 2012 John Wiley & Sons.

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.

A clinic-based study of 1063 patients with Type 2 diabetes recruited from 1973 to 1982 identified 533 deaths (attributed to coronary heart disease in 268 cases) by 31 December 1989. When compared to the general population of Australia the overall standardised mortality ratio was 1.42 (95 per cent confidence interval (CI) 1.26 to 1.58) for females and 1.19 (CI 1.03 to 1.35) for males. Cox regression analysis showed that having coronary heart disease or absence of foot pulses at the time of entrance to the study were the major independent risk factors for overall mortality after adjustment for initial age. Elevated cholesterol and blood pressure were found to be major independent risk factors for death from coronary heart disease.

Hypoglycaemia in patients with diabetes on nasogastric feeding is both potentially damaging and under-researched. We retrospectively reviewed 50 such inpatients to determine factors influencing hypoglycaemia. Our results showed 10.9% patient-days with ≥1 hypoglycaemic episode and 3.5% total blood glucose values

SummaryType 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised, controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C

In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n = 354; Type II, n = 392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P

Purpose This study aimed to address 2 questions: First, what are the existing summary statistics of frequency of hypoglycemia in insulin-treated adults on established nasogastric feeding in the general ward? Second, to what extent does lack of homogeneity in defining, identifying, and reporting hypoglycemia affect these statistics? Methods A systematic review of the literature documenting hypoglycemia in insulin-treated adults on nasogastric feeding for ≥ 3 days in the general ward was carried out. Data sources were PubMed, Embase, ProQuest, Cochrane, Directory of Open Access Journals, and PLoS. Search period was 1999 onward, postdating introduction of analog insulin. Results Initially, 231 studies were identified, with 9 judged suitable for inclusion, according to inclusion/exclusion criteria. All included studies had as their primary objective the assessment of efficacy of insulin/feed regimens in the target population. Studies exhibited major heterogeneity. Definitions of hypoglycemia varied from < 60 mg/dL (3.3 mmol/L) to < 80 mg/dL (4.4 mmol/L), and 5 methods of reporting frequency of hypoglycemia were utilized, precluding pooled analysis. A descriptive synthesis of results was generated with some comparable results presented on a modified forest plot, showing 2.1% to 10.2% of patients with a hypoglycemic event and 1.1% to 5.4% blood glucose level < 70 mg/dL (3.9 mmol/L). Conclusions Hypoglycemia is not uncommon in this population, but further research is needed for quantification. Standardized documentation and reporting methods incorporating sample size and study duration, such as hypoglycemic events per patient-days, would facilitate interstudy comparisons, as would documentation of hypoglycemia at the 2 most commonly defined levels: < 63 mg/dL (3.5 mmol/L) and < 70 mg/dL (3.9 mmol/L).

OBJECTIVE The triglyceride-lowering effects of ω-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g ω-3/day) and further randomized to a moderate (55–65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.

Background : Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. Aims : To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. Methods : In a prospective longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. Results : The prevalence of urine albumin of 30-300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L as compared to

In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n=354; Type II, n=392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P0.01), remaining significant when additionally adjusted for serum folate (P=0.043 and P=0.019 respectively). Serum folate was not clearly related to these events, although there was a trend to associate with the lower quintile of serum folate. The MTHFR genotype was not a determinant of plasma homocysteine, even in those in the lowest quintile of serum folate, nor of vascular disease. TT homozygosity at residue 677 was associated with elevation of total erythrocyte folate compared with both other genotypes (P0.0001), almost certainly due to the diversion of 5,10-methylenetetrahydrofolate into derivates subsequent to the partial metabolic block that results from the MTHFR enzyme defect. In conclusion, in this clinic cohort of people with diabetes, vascular disease is related to plasma homocysteine, which is correlated with serum folate. The MTHFR genotype does not significantly influence either plasma homocysteine or vascular disease, despite it being a determinant of erythrocyte folate, which reflects its effect on folate metabolism.

OBJECTIVE To determine the prevalence of latent pernicious anaemia (PA) in Type 1 diabetics. DESIGN Patients with Type 1 diabetes were screened at two yearly intervals on a continuing basis. SETTING Diabetic Unit, Royal Perth Hospital, Western Australia. PATIENTS Three hundred and seventy-one patients, 156 females and 215 males, attending a diabetic clinic. They were classified as having Type 1 diabetes on the basis of age of onset less than 40 years and requiring insulin from the start. MAIN OUTCOME MEASURES Serum cobalamin levels were measured and studies of thyroid function and a blood count were done. Patients with a reduced serum level of cobalamin had tests for cobalamin absorption. RESULTS Six patients had a low serum cobalamin level; five showed malabsorption of the vitamin which could be corrected by the addition of intrinsic factor. Four of these patients had no clinical signs of PA. The fifth was mildly anaemic (haemoglobin level 111 g/L) and had megaloblastic bone marrow. He was classified as having frank PA. The sixth patient was not available for further testing. These results give a prevalence of latent PA of 11 per 1000 in Type 1 diabetics, compared with 3.9 per 1000 in diabetics with clinically manifest disease and 1.27 per 1000 in the general population. All four patients with latent PA had hypothyroidism, based on low thyroxine levels, increased levels of thyroid stimulating hormone and the presence of thyroid antibodies. CONCLUSION Latent PA is not uncommon in Type 1 diabetics. It has a long preclinical course and occurs in those patients with thyroid disease. The screening of Type 1 diabetics for latent PA has worthwhile benefits as a "preventive" health measure.

This study assessed the effects of short-term circuit weight training (CWT) on glycaemic control in NIDDM. Twenty-seven untrained, sedentary subjects (mean age, 51) with NIDDM participated in an 8-week randomised, controlled study, involving either CWT 3 days/week (n = 15) or no formal exercise (control) (n = 12). All subjects performed regular self-blood glucose monitoring throughout. Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test (75 g) before and after 8 weeks. Twenty-one subjects completed the study (CWT, n = 11) (Control, n = 10). Strength for all exercises improved significantly after CWT. Pooled time-series analysis, using a random effects model, revealed an overall decrease in self-monitored glucose levels with CWT compared to controls. Significant reductions from baseline values were observed in both the glucose (-213 mmol l-1 per 120 min, P < 0.05) and insulin (-6130 pmol l-1 per 120 min, P < 0.05) area under the curve following CWT relative to controls. After adjustment for body mass changes, the change in self-monitored glucose levels and insulin area under the curve, but not glucose area under the curve, remained significant. Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition.

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.

In the present study, the determinants of fasting plasma homocysteine in diabetic subjects were examined; whether plasma homocysteine and vascular disease are related and the influence of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate, plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I, n = 354; Type II, n = 392) were recalled for a cross-sectional survey. Standard methods were used to measure biochemical variables and to characterize vascular disease and MTHFR genotype. Plasma homocysteine was significantly and directly related to age, male sex and serum urea, and inversely related to serum folate and vitamin B12, independently in stepwise regression. When corrected for age and sex, homocysteine was significantly related to hard end points of coronary artery disease and stroke (each P < 0.01), remaining significant when additionally adjusted for serum folate (P = 0.043 and P = 0.019 respectively). Serum folate was not clearly related to these events, although there was a trend to associate with the lower quintile of serum folate. The MTHFR genotype was not a determinant of plasma homocysteine, even in those in the lowest quintile of serum folate, nor of vascular disease. TT homozygosity at residue 677 was associated with elevation of total erythrocyte folate compared with both other genotypes (P < 0.0001), almost certainly due to the diversion of 5, 10-methylenetetrahydrofolate into derivates subsequent to the partial metabolic block that results from the MTHFR enzyme defect. In conclusion, in this clinic cohort of people with diabetes, vascular disease is related to plasma homocysteine, which is correlated with serum folate. The MTHFR genotype does not significantly influence either plasma homocysteine or vascular disease, despite it being a determinant of erythrocyte folate, which reflects its effect on folate metabolism.

Summary: Two cases of systemic cryptococcosis treated with 5-Fluorocytosine and the insertion of a ventriculostomy reservoir are reported. The effectiveness and complications of this therapy are discussed.

The prevalence of diabetic complications is reported from a cross-sectional study of rural diabetic subjects in Western Australia. Logistic-regression analysis has been used to discover potential risk factors associated with each complication. A distinction has been made between time-related variables (age, age at diagnosis, duration of diabetes) and other risk variables. We have attempted to identify the major time-related risk variables for each complication and then examined the effect of other risk variables after accounting for the major time-related variables. The important time-related variables were found to be duration of diabetes for retinopathy, age for macrovascular disease, duration and age at diagnosis of diabetes for sensory neuropathy, and age for renal impairment. When matched on these important time-related variables, the overall prevalences of complications for insulin-dependent (IDDM) compared wjth non-insulin-dependent (NIDDM) diabetic patients were essentially the same. An exception is renal impairment, for which IDDM patients had a higher prevalence than did NIDDM patients of the same age. After allowing for time-related variables, the analysis also demonstrates positive independent associations between diabetic control (glycosylated hemoglobin) and retinopathy and between diabetic control and macrovascular disease. Plasma cholesterol (positively) and high-density lipoprotein cholesterol (negatively) were related independently to both macrovascular disease and renal impairment. Very few differences in the risk-factor profiles for complications were found for IDDM compared with NIDDM patients after allowing for time-related variables.

1. The effect of dietary fish oil supplementation on serum lipids was examined in normolipidaemic insulin-dependent male diabetics and healthy controls. Fish oil was given as Max eicosapentaenoic acid (EPA), 15 g daily (equivalent to 2.7 g/day of EPA) for 3 weeks. 2. There was a substantial increase in EPA but a depletion of arachidonic acid content of platelet phospholipids. 3. Diabetics showed a rise in total cholesterol, attributable to increases in low density and high density lipoprotein (LDL and HDL) cholesterol. The rise in HDL cholesterol was largely due to an increase in its HDL2 subclass. Similar changes were found in the healthy men although these were not as marked. A decrease in triglycerides was observed in both diabetics and normal controls. 4. Generally, diabetics showed greater changes in lipid concentrations which may suggest an altered metabolic response to w3 fatty acids. Therefore, the possible detrimental effect of the rise in total cholesterol and LDL cholesterol following fish oil administration may be offset by the increase in the protective HDL2 subclass.

Summary: The mean glycosylated haemoglobin A, level in 200 diabetics, 13-2%±2–6 (1SD), was nearly twice the level found in 100 non-diabetics, 7–42%±0–6 (1SD), and overlap between the two populations was minimal. Glycosylated haemoglobin A, levels, fasting and two hour post-prandial blood glucose concentrations and 24 hour urinary glucose excretion were measured at intervals over a period of 12 weeks in six diabetics requiring stabilisation. A close correlation was found between glycosylated haemoglobin Ay levels and short term parameters of control.

The effect of daily dietary supplementation with fish oil on serum lipids and platelet total phospholipid fatty acids was examined in male normolipidemic insulin-dependent diabetics and normal controls. They were given 15 g/d of fish oil as Max EPA (equivalent to 2.7 g/d of eicosapentaenoic acid) for 3 weeks. The diabetics showed a rise in total cholesterol, attributable to increases in LDL- and HDL-cholesterol. The increase in HDL-cholesterol was largely due to a rise in its HDL2 subclass. There was also a decrease in triglycerides in both groups. Similar changes in lipids were seen in the normal controls, although these were not significant. The more pronounced effect in diabetics suggests an altered metabolic response to omega-3 fatty acids in that disorder. However, the results indicate that the possible detrimental effect of the rise in total and LDL-cholesterol following fish oil may be offset by the increase in the protective HDL2 subclass.