Search

Aim: To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes., Methods: This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks., Results: Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve., Conclusions: Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Objective: Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women., Research Design and Methods: A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity., Results: The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04)., Conclusions: Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.

Purpose: The aim of this study was to examine the associations among fasting insulin, adiposity, waist girth, and blood pressure among a nondiabetic multiethnic population., Methods: A cross-sectional study was performed among 25-44-year-old African-Americans (n = 159), Cuban-Americans (n = 128), and non-Hispanic whites (n = 207) selected from Dade County, Florida. Fasting insulin levels were correlated with resting blood pressure level within each ethnic group. The separate effects of percentage body fat and waist girth on the association between blood pressure and insulin were analyzed in multiple linear regression and analysis of covariance., Results: Fasting insulin was positively associated with systolic (r = 0.26-0.39; P < 0.01) and diastolic blood pressure (r = 0.19-0.30; P = 0.10 to P < 0.001) among women of all ethnic groups and among non-Hispanic white men (r = 0.27; P < 0.05). Stepwise linear regression analyses revealed statistically significant associations between systolic and diastolic blood pressure and fasting insulin level in non-Hispanic whites independent of other covariates, including sex and percentage body fat (P < 0.001). Fasting insulin was also independently and significantly related to systolic blood pressure among African-Americans (P = 0.02). Among Cuban-Americans, sex and percentage body fat were the main correlates of blood pressure level. Analysis of covariance revealed a relationship between insulin and blood pressure that was independent of waist girth among men and women., Conclusions: Fasting insulin level and blood pressure were positively associated among African-Americans and non-Hispanic whites. This association was not entirely due to the common association with percentage body fat or waist girth.

Objective: To assess sex and ethnic differences in hyperinsulinemia/insulin resistance and to examine the impact of percent body fat on such differences., Research Design and Methods: A cross-sectional epidemiological study was performed in a normoglycemic population of African-Americans (n = 159), Cuban Americans (n = 128), and non-Hispanic whites (n = 207) who resided in Dade County, Florida, from 1990 to 1995. The insulin area under the curve (AUC) in response to a standard 75-g oral glucose tolerance test (OGTT) was used as an indicator of hyperinsulinemia/insulin resistance. Analysis of covariance was performed to compare sex and ethnic differences in the insulin AUC. Multiple linear regression was used to evaluate the independent correlates of the insulin AUC., Results: After covariate adjustment for percent body fat, men displayed a significantly higher insulin AUC than did women (P < 0.001). African-Americans and Cuban-Americans each had a significantly higher insulin AUC than did non-Hispanic white participants (P = 0.01). Alcohol consumption was inversely related to AUC (P = 0.04)., Conclusions: Despite the greater percentage of body fat in women, the insulin AUC was similar in women and men. After adjustment for the sex difference in percent body fat, women displayed a lower insulin AUC than did men, indicating enhanced insulin sensitivity. These differences by sex and ethnicity in insulin resistance are consistent with established differences in heart-disease risk (i.e., higher in men and African-Americans) and suggest that hyperinsulinemia/insulin resistance may partly underlie such differences.

The interrelationships between body weight, insulin secretion and serum lipids were studied in 40 young white patients (mean age 37 years) with established ischemic heart disease (IHD), living in Johannesburg. None was severely obese, hypertensive or overtly diabetic. In general, strong positive correlations were found between body weight and insulin concentrations and between insulin levels and fasting serum triglycerides. However, insulin levels were relatively low in 4 patients with marked hypertriglyceridemia (above 350 mg/dl). These data are consistent with the postulate that insulin promotes (hepatic) triglyceride synthesis, but when there is gross hypertriglyceridemia peripheral triglyceride clearance becomes defective. Insignificant correlations were observed between body weight and serum lipids and between cholesterol and other metabolic variables. We conclude that there is a sequential link between increasing body weight, insulin secretion and triglyceride levels in young patients with IHD, but that cholesterolemia is independent of this axis.

Type I insulin-dependent diabetic patients have an increased risk of atherosclerotic vascular disease that may be determined in part by their tendency to develop circulating lipid and lipoprotein abnormalities. The occurrence of such findings in asymptomatic ambulant Type I patients with mild or moderate hyperglycemia might suggest that conventional methods of insulin treatment are as inefficient at normalizing lipid abnormalities as they are in achieving euglycemia. It would then be important to ascertain whether intensive methods of insulin treatment effectively normalized lipid levels. Ten insulin-dependent young adult diabetic patients were studied on a conventional insulin treatment regimen and then at two-monthly intervals for a six-month period during which they were managed by three different intensified insulin treatment regimens. Plasma glucose levels improved substantially (p less than 0.001) after two months of intensified therapy (106 +/- 4 mg/dl) and did not change significantly thereafter for the remaining four months of intensified insulin treatment. Apart from a short-lived decrease in total-, LDL- and HDL-cholesterol after two months of intensified treatment (baseline total triglyceride 116 +/- 13 mg/dl, total cholesterol 174 +/- 16 mg/dl, HDL-cholesterol 46 +/- 3 mg/dl). There were no persistent changes in serum lipids, lipoprotein cholesterol or in levels of their major apoproteins A-I, A-II and B. These findings support the contention that, despite moderate hyperglycemia, conventional insulin treatment may be adequate to maintain normal lipid levels. In such circumstances achievement of euglycemia by intensified insulin therapy leads to little change in circulating lipid and lipoprotein values.

Aspects of carbohydrate and lipid metabolism were studied in 50 nondiabetic African subjects living in Johannesburg. Twenty-six of them were overweight, invariably associated with a high-carbohydrate intake. In general, the obese group demonstrated significantly raised serum insulin levels, normal glucose tolerance, normal fasting serum triglycerides, and significantly elevated serum cholesterol concentrations. However, the degree of obesity was not significantly correlated with any of these metabolic variables--notably basal or stimulated insulin levels. This suggests that the obese state, per se, was not the major cause of the hyperinsulinemia, and that other factors influenced individual insulin responses or sensitivity. Inconsistently excessive dietary carbohydrate ingestion and an unusual degree of physical activity may have been important. A striking correlation emerged between fasting serum triglycerides and insulin concentrations (both basal and stimulated); the possibility that this reflects acceleration of hepatic triglyceride synthesis by insulin is discussed. The concept of obesity invariably producing insulin resistance and progressive compensatory hyperinsulinism may not apply in all environmental conditions.