The in utero environment is a powerful risk factor for type 2 diabetes in offspring, but little is known about the risk conveyed by nondiabetic gestational glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers and 1,436 of their children. Associations were assessed in multivariate models between maternal third trimester glucose tolerance and indexes of body composition and glycemic control in their children. At parturition, the mothers' ages ranged from 14 to 43 years. Offspring were studied at age 0 -39 years. An SD (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P ؍ 0.0002). This effect persisted when only offspring of normal glucose tolerant mothers were examined (57 g, P < 0.0001). 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). When only offspring of normal glucose tolerant mothers were examined, the risk was reduced but remained significant (1.3 [1.04 -1.71], P ؍ 0.026). In conclusion, maternal glycemia during pregnancy is associated with increased birth weight and risk of diabetes in Pima Indian offspring, even when mothers are normal glucose tolerant during pregnancy. Thus, prevention of offspring type 2 diabetes may require strategies that focus on improving gestational glucose tolerance even within the normal range. Diabetes 55: 460 -465, 2006 T he environment in which the fetus develops determines a considerable proportion of the risk of developing chronic metabolic disease during adulthood (1). Since in humans and other mammals the fetus is entirely dependent upon the supply of nutrients from the mother, maternal malnutrition or hyperglycemia can result in an in utero milieu that affects the growth and programming of fetal tissues and organs (2). In rodents, in utero hyperglycemia stimulates islet hyperplasia and -cell hyperactivity within the fetal endocrine pancreas (2). These pancreatic adaptations augment uptake of glucose and amino acids, which manifests as fetal macrosomia. Because of this nutritional excess and the consequential hyperinsulinemia, hormonal growth factor concentrations such as insulin-like growth factors increase (3), causing the offspring of diabetic mothers to be heavier for gestational age than the offspring of nondiabetic mothers (4). In addition, offspring of diabetic mothers incur a higher lifetime risk of type 2 diabetes and related complications (4 -6).Although a postchallenge glucose tolerance of 7.8 -11.0 mmol/l (140 -199 mg/dl) is conventionally used to determine impaired glucose tolerance, during pregnancy it is used to define gestational diabetes (7). Given the known effects of uncontrolled gestational diabetes on the growing fetus, treatment, usually in the form of dietary modification and/or insulin, is recommended above this threshold (8). However, the nature of the relationship between a nondiabetic mother's postchallenge glucose and the offspring's risk of type 2 diabetes has received lit...
OBJECTIVE -By age 5 years, offspring of diabetic mothers (ODMs) are heavier and have altered glucose metabolism compared with offspring of mothers without diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the age of 5 years.RESEARCH DESIGN AND METHODS -Anthropometric measures (z scores) from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by maternal diabetes status.RESULTS -After adjustment for earlier gestational age at delivery (37.8 vs. 39.3 weeks, P Ͻ 0.01), ODMs were heavier at birth (z score birth weight 0.49 vs. Ϫ0.04, P Ͻ 0.01) than non-DMs. At age 1.5 years, ODMs were shorter than the non-DMs (z score ϭ Ϫ0.24 vs. 0.12, P Ͻ 0.01) but their weight and relative weight (RW; weight adjusted for age, sex, and length or height) were similar. From birth to 1.5 years, ODMs showed significant "catch down" of weight compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs and non-DMs was Ϫ0.56 and 0.12, respectively, P Ͻ 0.01). By age 7.7 years, ODMs were heavier (weight z score 0.89 vs. Ϫ0.07, P Ͻ 0.01) but had similar height as non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were dependent on RW.CONCLUSIONS -ODMs had a dramatically different growth pattern from that of nonDMs. Gestational age-adjusted birth weight was higher. During the first 1.5 postnatal years, the change in weight z score and attained height were reduced. Subsequently, height caught up to that of non-DMs, while weight gain greatly exceeded that of non-DMs. Diabetes Care 28:585-589, 2005T here is an alarming increase in obesity and type 2 diabetes in children in the United States, particularly among high-risk populations such as Pima Indians (1). Because both of these disorders carry great morbidity and are so difficult to treat, understanding their pathogenesis in order to formulate treatment and prevention strategies is important.A number of anthropometric and personal characteristics have been identified as risk factors for obesity and diabetes. These attributes are at times difficult to reconcile. In the Pima Indian population, maternal diabetes during pregnancy, usually associated with higher offspring birth weight, carries an increased risk of diabetes and obesity in their children (2,3). Lower birth weight, however, is also associated with increased risk of later type 2 diabetes in both the Pima (4) and other populations (5). Individuals who develop type 2 diabetes in adult life in Caucasian (6) and Asian (7) populations have been found to have low BMI in the first 2 years of life but accelerated weight gain thereafter. By contrast, "catch-up" growth (upward crossing of centiles) in this same postnatal period (birth to age 2 years) has been associated with increased adiposity in childhood (8), which is in turn associated with early-onset diabetes (1). Breastfeeding, which does not alter the weight gain pattern of infants in the first 6 months of life (9), is associated with reduced risk of obesity and type 2 diabetes in some populations (1...
To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. RESEARCH DESIGN AND METHODSDPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ‡5 years of type 1 diabetes duration. A score of ‡4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. RESULTSAmong 5,936 T1D Exchange participants (mean 6 SD age 39 6 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA 1c ] 8.1 6 1.6% [65.3 6 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA 1c , had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P 5 0.008), hypertriglyceridemia (P 5 0.002), higher BMI (P 5 0.009), retinopathy (P 5 0.004), reduced estimated glomerular filtration rate (P 5 0.02), and Charcot neuroarthropathy (P 5 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P 5 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months. CONCLUSIONSThe prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.Diabetic neuropathy is a prevalent complication in patients with diabetes and a major cause of morbidity and mortality (1). Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathies are by far the most studied (1).
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