The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and their relationship to age and obesity was estimated in the rural town of Shikarpur in Sindh Province, Pakistan by a population-based survey in 1994. Self-administered questionnaires were used to obtain partial food frequency data. In that study, the sensitivity of the criteria was 24%, with a positive predictive value of 3%, i.e., 40 children needed to be tested to yield one abnormal result. 12-13 weeks old male Wistar rats (n = 6-7 per group) were treated by streptozotocin for 3 consecutive days, at dose of either 25 mg/kg/day i.p. Metabolic and hormonal characteristics of the GI group included significantly higher fasting and glucose-stimulated insulin levels, more severe insulin resistance, hyperandrogenemia, and significantly higher cortisol and androstenedione responses to 1–24 ACTH stimulation. Furthermore, both in pregnancy and at 3 months postpartum, insulin sensitivity (IS(OGTT)) and pancreatic beta-cell function (insulinogenic index/homeostasis model assessment of insulin resistance) progressively decreased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P(trend) < 0.0001). In this review we explore the available evidence linking OSA with IR, glucose intolerance and T2DM, and discuss potential pathobiological mechanisms by which sleep disordered breathing can affect metabolic health.
In Cox proportional hazards models, the adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose was 1.6 (95% CI 1.3-2.0, P < 0.0001). On multinomial logistic regression analysis, fasting plasma glucose at diagnosis of index GDM and duration lapse after index GDM were shown to be significantly higher in women with isolated impaired fasting glucose (IFG), combined IFG/impaired glucose tolerance and T2DM, as compared to women with normal glucose tolerance (p < 0.05). There was a significant relation between GGT and area under the curve (AUC) of oral glucose tolerance test (p = 0.00). The phenomenon of age-related glucose intolerance is the result of defects specific for the aging process and distinct and separate from those characterizing obesity and non-insulin-dependent diabetes; their distinguishing features are discussed. We calculated the antepartum DIo using the following measures: insulin secretion–sensitivity index-2 (ISSI-2) and insulinogenic index (IGI)/fasting insulin (5). Thus, lymph insulin, which may be reflective of interstitial fluid, is the signal to which insulin-sensitive tissues are responding. These studies support the concept that, at physiological insulin levels, the time for insulin to cross the capillary endothelium is the process that determines the rate of insulin action in vivo.
In separate experiments, a similar intimate relationship was found between lymph insulin and glucose utilization estimated from the minimal model, supporting the accuracy of the minimal model as a mathematical representation of insulin action in vivo. Additional factors in glucose tolerance are insulin secretion and clearance. We proposed a model of insulin/C-peptide kinetics, derived from the original conception of Eaton and Polonsky, in which determination of C-peptide kinetics in each individual is unnecessary if insulin and C-peptide kinetics are modeled simultaneously. Prehepatic insulin secretion after glucose injection was calculated in healthy women; total insulin secretion was 22.2 nmol; first-phase insulin averaged 38% of total, but there was wide variation among healthy subjects. The ability to determine insulin secretion, insulin action, and glucose effectiveness from modeling allowed us to investigate their interaction. The good news is that if prediabetes is diagnosed and treated promptly, hyperglycemia can be often be reversed, minimizing the risk of developing type 2 diabetes and other serious complications. Thus, with insulin resistance, it is proposed that a normal β-cell will increase its sensitivity to glucose appropriately, staving off impaired glucose tolerance.
This concept is supported by data in healthy pregnant women, in whom the reciprocal relationship is shown to exist and impaired glucose tolerance is not observed despite substantial insulin resistance (S, reduced to 1.8 × 10−4 min−1 · μU−1 · ml−1). Nancy's story is not unusual. Additionally, Pima Indians with the lowest sensitivity/secretion product appear to be at highest risk for developing NIDDM. This assay relies on the ApoPercentage dye that is selectively imported by apoptotic cells.22 Apoptotic cells developed red color following the intake of ApoPercentage dye and were detected under an inverted light microscope. Although no individual defect (≤80%) of these factors causes diabetic glucose tolerance (KG < 1), compound defects are remarkably synergistic, with a combined SI/SG defect being the most severe (KG = 0.60), and an SG defect being a requisite component for diabetic glucose tolerance.