A practical insulin infusion algorithm for the establishment of euglycaemia in both lean and obese patients with type 1 and type 2 diabetes.

BACKGROUND: Both in research and in various clinical situations, prolonged euglycaemia can be desirable. In recent years, its benefit in (critically) ill patients and patients with acute myocardial infarction has been established. The objective of this study was to assess safety and efficacy of a practical, bodyweight-dependent algorithm to establish euglycaemia in both lean and obese patients with type 1 and type 2 diabetes. METHODS: In 43 patients with type 1 diabetes and 17 patients with type 2 diabetes insulin were infused overnight to establish euglycaemia. Plasma glucose concentration was determined at 45 min intervals, and the insulin infusion rate was altered according to the algorithm. RESULTS: Baseline plasma glucose concentrations were 13.1+/- 4.4 and 12.7 +/- 4.0 mmol/l in type 1 and type 2 diabetic patients, respectively. In both groups mean plasma glucose was reduced below 8.0 mmol/l within 3 h, and averaged 7.4 +/- 1.4 and 7.2 +/- 1.0 mmol/l (P = 0.11) over the next 7 h. Five (11.6%) patients with type 1 diabetes required administration of glucose because plasma glucose concentrations fell below 4.4 mmol/l. Consequently, type 1 diabetic patients were hypoglycaemic during 0.89% of the total study period. The lowest plasma glucose recorded was 3.9 mmol/l. In the type 2 diabetic patients the lowest plasma glucose was 5.5 mmol/l and no glucose administration was required for near-hypoglycaemia. The algorithm was equally effective in both lean and obese patients. CONCLUSIONS: Euglycaemia was established simply, swiftly and safely during the study period with the practical weight-based algorithm used in this study, in both lean and obese type 1 and type 2 diabetic patients, with a very low rate of mild hypoglycaemia. The algorithm is applicable in research and various several clinical settings. Its validity for a prolonged period of time and in critically ill patients needs to be further evaluated.

Comparison of the accuracy of the HemoCue glucose analyzer with the Yellow Springs Instrument glucose oxidase analyzer, particularly in hypoglycemia.

OBJECTIVE: We aimed to assess the accuracy of the HemoCue Beta-glucose analyzer (HemoCue) and its correlation with the Yellow Springs Instrument (YSI 2300 STAT; YSI) glucose oxidase analyzer, in particular for hypoglycemic values. DESIGN AND METHODS: Samples were taken from 24 volunteers during hyperinsulinemic glucose clamp studies. Glucose concentrations were determined immediately with the HemoCue in whole blood and with the YSI in plasma from the same sample. After correction for the difference between whole blood and plasma, the paired plasma glucose concentrations were analyzed with various statistical methods. RESULTS: A total of 500 paired glucose values were obtained, 209 of which were in the hypoglycemic range. Mean+/-s.e. values were 4.85+/-0.004 mmol/l for the HemoCue (range 1.87-16.17) and 4.81+/-0.004 mmol/l for the YSI (range 1.88-15.00; P = 0.80). In the hypoglycemic region, values were 3.26+/-0.004 mmol/l for the HemoCue (range 1.87-5.17) and 3.22+/-0.003 mmol/l for the YSI (range 1.88-4.20; P = 0.59). Regression analyses were HemoCue = 1.019(YSI) -0.0577 mmol/l, with r = 0.9787 for all values; for hypoglycemic values the HemoCue = 1.1169(YSI) -0.3393 mmol/l, with r = 0.8798. Using Altman's residual plot, the difference was 0.03+/-0.0009 mmol/l, with 18 (3.6%) paired values outside the 95% limits of agreement (-0.82 to 0.89 mmol/l). In the hypoglycemic range, the difference was 0.04+/-0.001 mmol/l, with six (2.9%) values outside the 95% limits of agreement (-0.71 to 0.79 mmol/l). In error grid analysis, one value was in zone D (0.2%) and five values (1%) were in zone B; 98.8% were within zone A. CONCLUSIONS: Determination of glucose with the HemoCue system had very good correlation with the YSI system in a broad range of glycemia and also for hypoglycemic values. We believe that these methods can be used interchangeably for research and clinical purposes in adults.

Sex steroids and plasma lipoprotein levels in healthy women: The importance of androgens in the estrogen-deficient state.

The role of endogenous estrogens and androgens and their potential interaction in atherosclerosis is not well understood. Therefore, we investigated the effects of natural menopause and endogenous sex steroids on triglycerides (TG), a major risk factor for cardiovascular disease in women. Fasting lipid and lipoprotein concentrations, postheparin lipase activities, kinetic indicators of triglyceride lipolysis, and various hormone levels, including dehydroepiandrostenedione-sulfate (DHEA-S), (bioavailable) testosterone, and androstenedione, were determined in 18 premenopausal and 18 postmenopausal women, matched for age and body composition. Fasting plasma TG were 0.69 +/- 0.29 mmol/L in postmenopausal women and 0.73 +/- 0.33 mmol/L in premenopausal women (difference not significant [NS]). Approximately 30% of all plasma TG were present in the very-low-density lipoproteins (VLDLs) in both groups. No differences were found between groups in plasma lipolytic potential of TG-rich lipoproteins. Univariate analysis revealed that VLDL-TG concentrations were strongly related to insulin (r = 0.84, P =.0001) and androstenedione (r = 0.65, P =.004) in postmenopausal women. Multivariate analysis of potential determinants of VLDL-TG showed that insulin, androstenedione, and bioavailable testosterone were independent variables, explaining 87% of the variability (r = 0.93, P =.0001) in postmenopausal women. In contrast, in premenopausal women, the only identified predictor of fasting VLDL-TG in univariate and multivariate analysis was insulin (r = 0.72, P =.001). Our results show that the association of androgens with TG varied depending on androgen concentrations, the relative androgenic potential, and most importantly on hormonal milieu. Endogenous androgens were only related to plasma VLDL-TG in the estrogen-deficient state.

Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes.

OBJECTIVE: The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes. RESULTS: CETP TaqIB and A-629C polymorphisms were tightly concordant (P < 0.001). At baseline, B1B1 carriers had lower plasma HDL cholesterol (0.99 +/- 0.2 vs. 1.11 +/- 0.2 mmol/l, P < 0.05), higher CETP mass (2.62 +/- 0.8 vs. 2.05 +/- 0.4 mg/l, P < 0.001), and slightly increased, though not significant, plasma TGs (2.7 +/- 1.05 vs. 2.47 +/- 0.86, P = 0.34) compared with B2B2 carriers. Atorvastatin treatment significantly reduced CETP mass dose-dependently by 18% (A10) and 29% (A80; both vs. placebo P < 0.001, A10-A80 P < 0.001). CETP mass and activity were strongly correlated (r = 0.854, P < 0.0001). CETP TaqIB polymorphism appeared to modify the effect of atorvastatin on HDL cholesterol elevation (B1B1 7.2%, B1B2 6.1%, B2B2 0.5%; P < 0.05), TG reduction (B1B1 39.7%, B1B2 38.4%, B2B2 18.4%; P = 0.08), and CETP mass reduction (B1B1 32.1%, B1B2 29.6%, B2B2 21.9%; P = 0.27, NS). Similar results were obtained for the A-629C polymorphism. CONCLUSIONS: In conclusion, the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile, including low HDL, and they respond better to statin therapy. These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy.

Additional lunchtime basal insulin during insulin lispro intensive therapy in a randomized, multicenter, crossover study in adults : a real-life design.

OBJECTIVE: This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night. RESEARCH DESIGN AND METHODS: The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 x NPH) or twice (2 x NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA(1c) levels <8.5%. Efficacy measures were HbA(1c) levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials. RESULTS: In all, 104 patients completed the trial. The mean HbA(1c) level before randomization was 7.1 +/- 0.85%. The HbA(1c) levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] -0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 x NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 x NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively. CONCLUSIONS: Equal HbA(1c) levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 x NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.

Risk factors for coronary heart disease: implications of gender.

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show similar responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.

The sulfonylurea glyburide induces impairment of glucagon and growth hormone responses during mild insulin-induced hypoglycemia.

OBJECTIVE: The sulfonylurea (SU) glyburide may cause severe and prolonged episodes of hypoglycemia. We aimed at investigating the impact of glyburide on glucose counterregulatory hormones during stepwise hypoglycemic clamp studies. RESEARCH DESIGN AND METHODS: We performed stepwise hypoglycemic clamp studies in 16 healthy volunteers (7 women and 9 men aged 44 +/- 10 years). We investigated counterregulatory hormonal and symptom responses at arterialized venous plasma glucose levels (PG) of 3.8, 3.2, and 2.6 mmol/l, comparing 10 mg glyburide orally and placebo in a double-blind, randomized crossover fashion. RESULTS: The increase in plasma glucagon with time from PG = 3.8 onward was smaller for glyburide than for placebo (P = 0.014). Plasma glucagon area under the curve (AUC)(60-180) was lower after glyburide than after placebo (1,774 +/- 715 vs. 2,161 +/- 856 pmol. l(-1). min, P = 0.014). From PG = 3.8 onward, plasma growth hormone (GH) levels with placebo were nearly two times (1.9 [95% CI 1.2-2.9]) as high as with glyburide (P = 0.011). AUC(60-180) for GH was lower after glyburide than after placebo (geometric mean [range] 665 [356-1,275] and 1,058 [392-1,818] mU. l(-1). min, respectively; P = 0.04). No significant differences were observed for plasma cortisol, epinephrine and norepinephrine, or incremental symptom scores. CONCLUSIONS: The SU glyburide induces multiple defects in glucose counterregulatory hormonal responses, notably decreases in both glucagon and GH release.