Impact of maternal obesity and diabetes on long-term health of the offspring.

The initial observations of David Barker, popularly known as the “Barker hypothesis” or “developmental origins of health and disease,” show that being born with low birth weight, as a result of intrauterine growth restriction produced by maternal undernutrition, is associated with a number of chronic diseases later in life [1]. Subsequently, studies show that it is not just intrauterine growth restriction, but also exposure to any other adverse factor during fetal and/or early postnatal development that can increase susceptibility to a number of chronic diseases later in life including cardiovascular and renal disease, hypertension, type 2 diabetes, certain forms of cancer, osteoporosis, Parkinson’s disease, dementia, and polycystic ovary syndrome [2–4

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes

Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p <0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age +/- 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (<mean age-2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.Peer reviewe

Growth hormone exacerbates diabetic renal damage in male but not female rats

BACKGROUND: Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT(1)R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes. METHODS: Adult male and female Sprague–Dawley rats were injected with vehicle (control), STZ, or STZ + GH and euthanized after 8 weeks. RESULTS: Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-β expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-β protein in diabetic females, GH increased TGF-β protein in the male rat’s kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT(1)R activity. CONCLUSIONS: These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators

Amlodipine Reduces Inflammation despite Promoting Albuminuria in the Streptozotocin-Induced Diabetic Rat

Amlodipine reduces blood pressure; however, its effect in the diabetic kidney irrespective of its blood pressure-lowering effects is unclear. This study examined the effects of amlodipine (0, 5, 10 and 20 mg/kg; DA0, DA5, DA10 and DA20, respectively) for 12 weeks on renal functional and structural changes in the streptozotocin-induced diabetic rat, a nonhypertensive model of diabetes-associated hyperfiltration. Compared with nondiabetic rats, diabetes (D) was associated with increased urine albumin excretion (UAE, 12.6 ± 3.40 vs. 3.73 ± 1.14 mg/day), glomerular filtration rate (2.17 ± 0.09 vs. 1.64 ± 0.12 ml/min/g kidney weight), glomerulosclerosis (0.21 ± 0.03 vs. 0.05 ± 0.01 AU) and infiltration of inflammatory cells (18.5 ± 2.78 vs. 6.92 ± 0.70 cells/cm2), but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg). While DA20 abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight) and inflammatory cell abundance (6.0 ± 0.79 cells/cm2), it exacerbated UAE (43.5 ± 8.49 mg/day) and increased MAP (132 ± 3.76 mm Hg), but had no effect on renal pathology. These data suggest that amlodipine reduces renal inflammation and abolished glomerular hyperfiltration, but increases blood pressure and exacerbates albuminuria in the rat model of normotensive diabetic kidney disease. We conclude that amlodipine may have limited renoprotective effects in the face of hyperfiltration and absence of elevated blood pressure