Search

Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances. Plain Language Summary: Plain language summary is available for this article. [ABSTRACT FROM AUTHOR]

Aims: Little is known regarding initiation of insulin therapy in type 2 diabetes (T2D) in Central and South-Eastern European countries. Therefore, we conducted a survey to characterise the prescribing practices of specialist diabetes healthcare professionals in this region and assessed factors that influence clinical decision-making regarding insulin initiation in T2D. Methods: A cross-sectional survey sampled 211 specialist diabetes healthcare prescribers from five Central and South-Eastern European countries (Bulgaria, Croatia, Greece, Hungary, and Slovenia). A structured questionnaire was developed which surveyed current clinical practices and influencing factors, barriers to insulin initiation, and combination therapy prescribing preferences. Result: Only 9.4% (20 of out of 211 respondents) of healthcare professionals would initiate insulin therapy in T2D patients at the recommended HbA1c threshold of 7–7.9% [53–63 mmol/mol]. Large regional differences were evident in insulin initiation thresholds (≥ 9.0% [≥ 75 mmol/mol]: Bulgaria 80.8% vs. Slovenia 13.3%). Psychological distress was recorded as the major barrier to insulin initiation. Health insurance regulations were ranked more important than personal clinical experience and clinical guidelines in clinical decision-making. Information from peers was more influential than manufacturer information, clinical experience, and continuous medical education, respectively, for insulin initiation. Conclusions: Despite large regional variation, there is widespread delay of insulin initiation from specialist diabetes healthcare professionals in Central and South-Eastern Europe. [ABSTRACT FROM AUTHOR]

Purpose: There is limited and inconsistent evidence regarding longitudinal effects of macronutrients on blood pressure (BP) haemodynamics and arterial aging in populations without cardiovascular disease (CVD). We aimed to prospectively investigate potential association of dietary macronutrients with long-term changes in peripheral and central haemodynamics and arterial stiffness. Methods: One hundred and fifteen subjects (46.7 ± 8.73 years, 70 women), free of clinically overt CVD were consecutively recruited. Dietary macronutrient intake was evaluated using 3-day food records at baseline. Aortic stiffness and arterial wave reflections were assessed at baseline and in one follow-up visit 5 years later by pulse wave velocity (PWV) and augmentation index (AI), respectively. Results: Individuals with the highest consumption of saturated fatty acids (SFA) presented the highest rate of progression in PWV, AI and aortic diastolic BP (p < 0.05 for all) after adjustment for age, gender, smoking, body mass index, hyperlipidemia, insulin resistance, changes in systolic BP and treatment with antihypertensive and hypolipidemic drugs. After similar multivariable adjustments, high consumption of carbohydrates was associated with higher progression of AI, whereas high consumption of monounsaturated fatty acids (MUFA) and fibre with lower progression in aortic and peripheral systolic and diastolic BP (p < 0.05 for all). Conclusions: In subjects without CVD, high consumption of SFA is related to accelerated arterial stiffening, while high consumption of MUFA and fibre and low intake of carbohydrates is associated with attenuated progression in blood pressure and arterial wave reflections, respectively. These findings expand current knowledge on the association of macronutrient consumption with arterial aging in the general population. [ABSTRACT FROM AUTHOR]

Purpose: Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function. Methods: Ten young, healthy males participated in this crossover study (age: 24.3 ± 2.3 year; weight: 80.8 ± 5.3 kg; BMI: 24.3 ± 0.4 kg m). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low-intensity intermittent walking exercise to achieve hypohydration of −2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded. Results: Hypohydration by −1.9 ± 0.1 % of body mass resulted in decreased plasma volume by −3.5 ± 1.8 % and increased plasma osmolality by 9 ± 2 mmol kg ( P < 0.001). FMD as a response to hypohydration decreased by −26.8 ± 3.9 % ( P < 0.05). Conclusion: The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function. [ABSTRACT FROM AUTHOR]

Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. We measured IR [by a euglycaemic–hyperinsulinaemic (240 pmol min−1 m−2) clamp technique] in 1,296 non-diabetic (on a 75 g OGTT) individuals [716 women and 579 men, mean age 44 years, BMI 26 kg/m2 (range 18–44 kg/m2)] recruited at 19 centres in 14 European countries. IR was related to fasting proinsulin or pancreatic glucagon concentrations in univariate and multivariate analyses. Given its known relationship to IR, serum adiponectin was used as a positive control. In either sex, both glucagon and proinsulin were directly related to IR, while adiponectin was negatively associated with it (all p < 0.0001). In multivariate models, controlling for known determinants of insulin sensitivity (i.e . sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR. Finally, when these associations were tested as the probability that individuals in the top IR quartile would have hormone levels in the top quartile of their distribution independently of covariates, the odds ratio was ∼2 for both glucagon ( p = 0.05) and proinsulin ( p = 0.02) and 0.36 for adiponectin ( p < 0.0001). Whole-body IR is independently associated with raised fasting plasma glucagon and proinsulin concentrations, possibly as a result of IR at the level of alpha cells and beta cells in pancreatic islets. [ABSTRACT FROM AUTHOR]

Based on the known action of xanthine derivatives on the insulin secretion, the effect of pentoxifylline on carbohydrate homeostasis of type I (IDDM) and type II (NIDDM) diabetics was investigated. Pentoxifylline is known to exert a favorable influence on hemorheological disturbances in such patients. Twenty-four hour blood glucose pattern and insulin requirements were evaluated in type I and type II diabetics by the use of the artificial pancreas before and after a 14-day treatment with pentoxifylline 400 mg p.o. (Trental 400) t.i.d. During the stabilization period before treatment with pentoxifylline, NIDDM patients required 10.1±3.8 U of insulin and the IDDM 35±13.7 U. After 2 weeks on pentoxifylline, NIDDM required only 6.3±2.8 U (p<0.05) and IDDM 28.5±9.7 U (n.s.). Average blood glucose during the 24h decreased by 15.8±3.5% in NIDDM and by 10.3±2.5% in IDDM. Moreover, a significant smoothing of glucose fluctuations during the 24h was noted in both groups. It is concluded that pentoxifylline administered concurrently to any antidiabetic type of treatment leads to better blood glucose control as well as to prevention or delay of vascular complications. [ABSTRACT FROM AUTHOR]

BAYo1248 and BAYm1099 are two new α-glucosidase inhibitors. Postprandial glucose tolerance was significantly improved and post-prandial insulin requirements were significantly reduced as compared to placebo after breakfast and lunch when 20 mg BAYo1248 were administered prior to breakfast and after breakfast, lunch and dinner when 50 mg BAYm1099 were given prior to all three main meals. Postprandial breath H concentrations were mildly increased when these α-glucosidase inhibitors were given and no patient complained of any adverse effects (such as flatulence, abdominal pain or diarrhea). BAYo1248 and BAYm1099 might be useful adjuncts to insulin in the treatment of patients with insulin-dependent diabetes mellitus. [ABSTRACT FROM AUTHOR]

According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although many animal and in vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney in the postabsorptive state has generally been regarded as negligible. This traditional view is based on net balance measurements which, other than after a prolonged fast or during metabolic acidosis, showed no significant net renal glucose release. However, recent studies have refuted this view by combining isotopic and balance techniques, which have demonstrated that renal glucose production accounts for 25 % of systemic glucose production. Moreover, these studies indicate that glucose production by the human kidney is stimulated by epinephrine, inhibited by insulin and is excessive in diabetes mellitus. Since renal glucose release is largely, if not exclusively, due to gluconeogenesis, it is likely that the kidney is as important a gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactate, glutamine and glycerol. The implications of these recent findings on the understanding of the physiology and pathophysiology of human glucose metabolism are discussed. [Diabetologia (1997) 40: 749–757]. [ABSTRACT FROM AUTHOR]