CiteULike: omalbams diabetestype1

Sex Hormone-Binding Globulin and Testosterone in Individuals With Childhood Diabetes

Kirstie Danielson — 2008-05-29T19:11:23-00:00

Diabetes Care, Vol. 31, No. 6. (1 June 2008), pp. 1207-1213.

OBJECTIVE--Insulin downregulates hepatic production of sex hormone-binding globulin (SHBG), which in turn influences sex hormone bioavailability. The effects of childhood-onset diabetes and insulin resistance in nondiabetic individuals on SHBG and testosterone in children and young adults are poorly understood. RESEARCH DESIGN AND METHODS--Individuals with diabetes diagnosed at <18 years of age (n = 48) and their siblings without diabetes (n = 47) were recruited for the Chicago Childhood Diabetes Registry Family Study. SHBG and total and free testosterone were measured. Participants ranged in age from 10 to 32 years; 39% were non-Hispanic white. The majority of individuals with diabetes had the classic type 1 phenotype (75%), while the remainder exhibited features of type 2 or mixed diabetes; 96% were treated with insulin. RESULTS--SHBG and total testosterone were higher in male subjects with diabetes compared with those in male siblings. Elevated SHBG was associated with the absence of endogenous insulin independent of sex; elevated total testosterone was similarly associated with the absence of C-peptide for male subjects only. Diabetes type and treatment were unrelated. In those without diabetes, greater insulin resistance had a small, nonsignificant association with lower SHBG and higher free testosterone. CONCLUSIONS--SHBG and total testosterone appear to be higher in male children and young adults with diabetes compared with nondiabetic male siblings, which is apparently related to the absence of endogenous insulin. This may have implications for sex hormone-dependent processes across the lifespan in male individuals diagnosed with diabetes as children. 10.2337/dc07-2169

Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study

Rakesh Amin — 2008-03-19T15:57:22-00:00

BMJ (18 March 2008), bmj.39478.378241.BE.

Objectives To describe independent predictors for the development of microalbuminuria and progression to macroalbuminuria in those with childhood onset type 1 diabetes. Design Prospective observational study with follow-up for 9.8 (SD 3.8) years. Setting Oxford regional prospective study. Participants 527 participants with a diagnosis of type 1 diabetes at mean age 8.8 (SD 4.0) years. Main outcome measures Annual measurement of glycated haemoglobin (HbA1c) and assessment of urinary albumin:creatinine ratio. Results Cumulative prevalence of microalbuminuria was 25.7% (95% confidence interval 21.3% to 30.1%) after 10 years of diabetes and 50.7% (40.5% to 60.9%) after 19 years of diabetes and 5182 patient years of follow-up. The only modifiable adjusted predictor for microalbuminuria was high HbA1c concentrations (hazard ratio per 1% rise in HbA1c 1.39, 1.27 to 1.52). Blood pressure and history of smoking were not predictors. Microalbuminuria was persistent in 48% of patients. Cumulative prevalence of progression from microalbuminuria to macroalbuminuria was 13.9% (12.9% to 14.9%); progression occurred at a mean age of 18.5 (5.8) years. Although the sample size was small, modifiable predictors of macroalbuminuria were higher HbA1c levels and both persistent and intermittent microalbuminuria (hazard ratios 1.42 (1.22 to 1.78), 27.72 (7.99 to 96.12), and 8.76 (2.44 to 31.44), respectively). Conclusion In childhood onset type 1 diabetes, the only modifiable predictors were poor glycaemic control for the development of microalbuminuria and poor control and microalbuminuria (both persistent and intermittent) for progression to macroalbuminuria. Risk for macroalbuminuria is similar to that observed in cohorts with adult onset disease but as it occurs in young adult life early intervention in normotensive adolescents might be needed to improve prognosis. 10.1136/bmj.39478.378241.BE

Type 1 Diabetes Associated with Acquired Generalized Lipodystrophy and Insulin Resistance: The Effect of Long-Term Leptin Therapy

Jean Park — 2008-01-10T23:08:56-00:00

J Clin Endocrinol Metab, Vol. 93, No. 1. (1 January 2008), pp. 26-31.

Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Objective: Our objective was to describe the response to leptin therapy in patients with coexisting AGL and T1D and to document the autoimmune diseases associated with AGL. Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Results: Two patients had both AGL and T1D. The first was diagnosed with T1D at age 8 yr. Beginning at age 11 yr, he developed generalized lipodystrophy, elevated transaminases, and poor glycemic control [hemoglobin A1c (HbA1c) 10.7%] despite markedly increased insulin requirements (3.35 U/kgmiddle dotd). Further evaluation revealed hypoleptinemia and hypertriglyceridemia. At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U/kgmiddle dotd, his glycemic control improved (HbA1c 8.4%), and both his triglycerides and transaminases normalized. The second patient developed concurrent AGL and T1D at age 6 yr. Despite insulin doses of up to 32 U/kgmiddle dotd, she developed poor glycemic control (HbA1c 10.6%), hypertriglyceridemia (2984 mg/dl), elevated transaminases, and nonalcoholic steatohepatitis. At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA1c 7.3%) and her insulin requirements decreased (17 U/kgmiddle dotd). Her triglycerides remained elevated but were improved (441 mg/dl). Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL. 10.1210/jc.2007-1856