Nail-fold capillary hypertension may develop early in the course of diabetes, before the emergence of microvascular disease, and may be influenced by changes in metabolic control.

Background: Insulin resistance (IR) is the hallmark of PCOS and it is known that exercise may decrease it. What is unknown is whether exercise may mechanistically alter the underlying IR, attenuating the dynamic lipid induced IR in insulin resistant subjects.Methods: 12 women with polycystic ovary syndrome (PCOS) and 10 age and body mass index matched controls completed an 8 week supervised exercise program at 60% maximal oxygen consumption. Before and after the exercise program, all participants underwent hyperinsulinaemic euglycaemic clamps with either saline or intralipid infusions. Skewed data were log transformed and expressed as mean ± SEM.Results: Before exercise, women with PCOS had a higher HOMA-IR and lower VO2 max than controls. Compared to saline, lipid infusion lowered the rate of insulin stimulated glucose disposal (M value; mg/kg/min) by 67 ± 5% (from 0.5 ± 0.03 to −0.25 ± 0.2, p = 0.01) in PCOS, and by 49 ± 7% (from 0.65 ± 0.06 to 0.3 ± 0.1, p = 0.01) in controls. The M value was significantly less in PCOS compared to controls for both saline (p < 0.01) and lipid (p < 0.05). Endurance exercise in PCOS improved VO2 max and HOMA-IR, but not weight, to those of pre-exercise control subjects. The glucose disposal rate during the lipid infusion was reduced following exercise in PCOS, indicating decreased IR (67 ± 5 vs. 50 ± 7%, p = 0.02), but IR was not altered in controls (49 ± 7 vs. 45 ± 6%, p = 0.58). The incrementally increased IR induced by the lipid infusion did not differ between controls and PCOS.Conclusion: Insulin sensitivity improved with exercise in the PCOS group alone showing that IR can be modified, though likely transiently. However, the maximal IR response to the lipid infusion did not differ within and between control and PCOS subjects, indicating that the fundamental mechanism underlying insulin resistance was unchanged with exercise.Precis: Maximal insulin resistance induced by lipid infusion determined at baseline and 8 weeks after exercise in control and PCOS women did not differ, though insulin sensitivity increased in PCOS after exercise.

BackgroundAtherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS.Methods and ResultsFollowing overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P‐selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg−1 min−1, P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg−1 min−1, P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid‐induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS.ConclusionAcute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero‐thrombotic risk.Clinical Trial RegistrationURL: www.isrctn.org. Unique Identifier: ISRCTN42448814.

OBJECTIVE -Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women.RESEARCH DESIGN AND METHODS -Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n ϭ 8) were given a meal containing the stable isotope 1,1,1-13 C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of 13 C-palmitic acid ( 13 C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of 13 C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of 13 CO 2 in the breath denote more efficient of oxidation of dietary-derived lipid.RESULTS -In diabetic women, there were no differences between the pre-and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower CONCLUSIONS -The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women. Diabetes Care 26:3243-3249, 2003P atients with type 2 diabetes have an increased cardiovascular risk, which is particularly marked in diabetic women (1). In the nondiabetic population, women are relatively protected against coronary heart disease (CHD) when compared with men, an effect attributed to the physiological effects of estrogens (2,3). In contrast, diabetic women have an equivalent rate of CHD to diabetic men, appearing to lose the protection of estrogens (1).There are many contender mechanisms to account for the high CHD risk observed in diabetes (4), including diabetic dyslipidemia, which is thought to be particularly atherogenic and is characterized by fasting hypertriglyceridemia, low HDL cholesterol, and small dense LDL (4). The impact of the postprandial triglyceride load will be underestimated by examining fasting triglyceride values, as the typical western diet and pattern of feeding usually results in maintenance of the postprandial state for ϳ16 h each day (5). Postprandial triglyceride levels are determined by the metabolism of chylomicrons and VLDL. Chylomicrontriglyceride is hydrolyzed by the action of the enzyme lipoprotein lipase (LPL) releasing nonesterified fatty acids (NEFAs), the remaining chylomicron remnants being taken up by the liver via LDL receptors (6). Premenopausal nondiabetic women have been shown to have lower postprandial triglyceride levels than postmenopausal women (7,8), probably due to upregulation of hepatic LDL receptor by estrogens (9), thus increasing chylomicron remnant clearance. However, reduced chylomicron clearance is a feature of diabetes (10).We hypothesized that impaired clearance of circulatin...

1. Thinness at birth is associated with insulin resistance in adult life and an apparent delay in activation of glycolysis/glycogenolysis in exercising skeletal muscle. As developmental abnormalities of skeletal muscle histology or metabolism may explain this association we examined muscle histology, biochemistry and blood flow in a group of 27 adult women whose birth details were known. 2. Subjects were examined by near-infrared spectroscopy to determine forearm muscle oxygen supply, and by muscle biopsy and forearm plethysmography. Those with a ponderal index at birth < 23 kg/m3 were insulin resistant (assessed by the short insulin-tolerance test-mean rate constants for glucose disappearance = 4.14 compared with 4.83%/min, P = 0.045) and had significantly more rapid muscle reoxygenation than the remainder of the subjects (13 compared with 22 s, P = 0.004). 3. Thinness at birth did not influence muscle capillary density, muscle glycogen content, glycogen synthase activity, citrate synthase activity or resting forearm blood flow. 4. Insulin resistance seen after fetal malnutrition was not associated with abnormal muscle histology, resting muscle blood flow, mitochondrial volume or glycogen content. 5. The increase in muscle reoxygenation rate in adult subjects who were thin at birth could occur to promote oxidative ATP synthesis in compensation for the delay in activation of glycolysis/glycogenolysis. It suggests altered regulation rather than structure of the muscle microcirculation. These changes appear to antedate the structural and biochemical changes seen in muscle from patients with established diabetes.