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OBJECTIVE--Gestational diabetes is a risk factor for large-for-gestational-age (LGA) newborns, but many LGA babies are born to mothers with normal glucose tolerance. We aimed to clarify the association of maternal [...]

OBJECTIVE--The study was to determine whether being the macrosomic offspring of a mother without detected glucose intolerance during pregnancy has an impact on lipid profile, glucose homeostasis, and blood pressure [...]

The objective of this study was to establish the baseline retinal hemodynamic characteristics of stratified groups of diabetic patients at increasing risk for the development of diabetic macular edema (DME). Group 1 had 50 control subjects, group 2 had 56 diabetic patients without clinically visible retinopathy, group 3 had 54 diabetic patients with microaneurysms and/or hard exudates within two disc diameters of the fovea in the absence of clinically manifest DME, and group 4 had 40 patients with clinically manifest DME. Retinal hemodynamics (diameter, velocity, maximum-to-minimum velocity ratio, and flow) were assessed. Intraocular pressure, blood pressure, and relevant systemic markers of diabetes control and complications were also undertaken. The maximum-to-minimum velocity ratio was elevated with increasing risk of clinically significant DME (P < 0.0001). No significant differences were found between the groups with respect to diameter, velocity, or flow. The maximum-to-minimum velocity ratio was correlated to age, duration of diabetes, blood pressure, pulse rate, intraocular pressure, and serum potassium levels. In conclusion, the maximum-to-minimum velocity ratio was significantly increased with increasing risk of development of DME. Retinal arteriolar hemodynamics were positively correlated to age, duration of diabetes, and blood pressure. These findings suggest a reduction in the compliance (i.e., an increase of vascular rigidity) of the arteriolar circulation with increasing risk of DME., Diabetic retinopathy is a leading cause of visual impairment in the world, including North America (1). Due to the increasing prevalence of diabetes, the financial, societal, and personal burden of [...]

Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means ± SE from 13.5 ± 0.62 to 9.8 ± 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21% (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34% (P < 0.008) during the insulin suppression test and by 21% (P < 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR., In insulin-resistant individuals, glucose homeostasis can be maintained if the defect in insulin action is adequately compensated for by an increase in insulin concentration. This is achieved by a shift [...]

To shed further light on the primary alterations of insulin secretion in type 2 diabetes and the possible mechanisms involved, we studied several functional and molecular properties of islets isolated from the pancreata of 13 type 2 diabetic and 13 matched nondiabetic cadaveric organ donors. Glucose-stimulated insulin secretion from type 2 diabetic islets was significantly lower than from control islets, whereas arginine- and glibenclamide-stimulated insulin release was less markedly affected. The defects were accompanied by reduced mRNA expression of GLUT1 and -2 and glucokinase and by diminished glucose oxidation. In addition, AMP-activated protein kinase activation was reduced. Furthermore, the expression of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and forkhead box O1 (Foxo-1) was increased. Nitrotyrosine and 8-hydroxy-2'-deoxyguanosine concentrations, markers of oxidative stress, were significantly higher in type 2 diabetic than control islets, and they were correlated with the degree of glucose-stimulated insulin release impairment. Accordingly, 24-h exposure to glutathione significantly improved glucose-stimulated insulin release and decreased nitrotyrosine concentration, with partial recovery of insulin mRNA expression. These results provide direct evidence that the defects of insulin secretion in type 2 diabetic islets are associated with multiple islet cell alterations. Most importantly, the current study shows that the functional impairment of type 2 diabetic islets can be, at least in part, reversible. In this regard, it is suggested that reducing islet cell oxidative stress is a potential target of human type 2 diabetes therapy., Diabetes is a chronic metabolic syndrome caused by insulin deficiency. There are ~200 million diabetic individuals in the world, with only about half being diagnosed, and these numbers are expected [...]

Free fatty acids (FFAs) and glycerol oscillate in plasma. This study examined intrinsic lipolytic oscillations within adipocytes. Rat adipocytes were perifused with Krebs-Ringer bicarbonate buffer: 1) ± 2 mmol/l glucose; 2) +1 µmol/l isoproterenol ± 2 mmol/l glucose; 3) + increasing oleate; and 4) + increasing percent BSA. At 2 mmol/l glucose, there were 9 ± 1 glycerol, FFAs, and lactate pulses per hour with a pulse duration of 5 ± 1 mill. Lipolytic stimulation caused a 50-80% increase in the amplitude of lipolytic oscillations. Removal of glucose caused a 40-70% decrease in the amplitude of lipolytic oscillations and disturbed the pulsatility. Exogenous FFAs suppressed lipolysis and oscillatory amplitude, possibly because of increased cytosolic longchain coenzyme A (LC-CoA). Increasing percent BSA increased stimulated lipolysis and oscillatory amplitude, possibly because of decreased intracellular LC-CoA. These data show, for the first time, intrinsic lipolytic oscillations, which are glucose dependent and modulated by FFAs. We hypothesize that lipolytic oscillations are driven by oscillatory glucose metabolism, which leads to oscillatory relief of LC-CoA inhibition of triglyceride lipase(s). The results contribute to the understanding of physiological and biochemical regulators of lipolysis, such as glucose and FFAs. Lipolytic oscillations may be beneficial in the delivery of FFAs to liver, pancreas, and other tissues., Abnormal fat metabolism plays an important role in the pathogenesis of obesity-related type 2 diabetes (1-4), and elevated plasma free fatty acid (FFA) concentrations are associated with peripheral and hepatic [...]

OBJECTIVE--This article tests the hypothesis that women with impaired glucose tolerance (IGT) have the same pregnancy outcomes as those of their counterparts with normal glucose tolerance. RESEARCH DESIGN AND METHODS--From [...]

OBJECTIVE -- Differences in risk of erectile dysfunction (ED) by characteristics of diabetes among older men are not well understood. We examined the association of type and duration of diabetes [...]

OBJECTIVE -- Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently [...]

In an effort to better understand the phenomenon of lipotoxicity in human β-cells, we evaluated the effects of 48-h preculture with 1.0 or 2.0 mmol/l free fatty acid (FFA) (2:1 [...]

OBJECTIVE -- The interlead variation in duration of the Q-T interval on the surface electrocardiogram (Q-T interval dispersion [QTd]) has been shown to predict mortality in type 2 diabetic patients. [...]

OBSERVATIONS Improvement of Asthma After Administration of Pioglitazone We describe the case of a 71-year-old man who was being followed as an outpatient for type 2 diabetes, hyperlipidemia, hypertension, and [...]

Insulin concentrations oscillate at a periodicity of 5-15 min per oscillation. These oscillations are due to coordinate insulin secretory bursts, from millions of islets. The generation of common secretory bursts [...]

Human pancreatic islets from eight donors were incubated for 48 h in the presence of 2.0 mmol/l free fatty acid (FFA) (oleate to palmitate, 2 to 1). Insulin secretion was [...]

The mechanisms driving the pulsatility of insulin secretion in vivo and in vitro are still unclear. Because glucose metabolism and changes in cytosolic free [Ca.sup.2+] ([[[Ca.sup.2+]].sub.c]) in β-cells play a [...]

OBJECTIVE -- Clinical proteinuria is a risk factor for both end-stage renal disease and cardiovascular disease. The prevalence of clinical proteinuria, its correlates and predictive value, and the effect of [...]