Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis

Abstract

Objective: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. Design and methods: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values !0.05 were considered statistically significant. Results: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. Conclusions: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

“…The impairment in glucose metabolism, characterized by insulin resistance and mainly due to increased BMI and impaired body composition, has been often reported in GHD [6,44,45], but discordant data have been shown as regards the effect of GHT on it [35]. In our cohort of subjects we found that the GHD group did not differ significantly from the control group for fasting glucose, insulin and HbA1c levels and that these parameters did not significantly change during GHT.…”

Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice

“…The reciprocal changes in these endpoints, observed in AOiGHD mice, coupled with the fact that AOiGHD mice exhibit postprandial hypertriglyceridemia (7), indicate that insulin's actions on the liver may be reduced. Given these studies were performed in mouse models with isolated changes in endogenous GH levels and weight was controlled by diet, we might speculate impaired hepatic function represents an early metabolic defect in AOGHD patients that could serve to promote the progression to diabetes if caloric intake is in excess (1). In addition, the positive effect of GH on liver function may serve to offset the negative effects of GH on muscle insulin sensitivity, serving to control glucose homeostasis when low-dose GH replacement therapy is applied.…”

“…AOGHD patients can show reduced (5), normal (12), or elevated (8) insulin levels. A wide spectrum of insulin sensitivity in AOGHD patients may be in part due to the length, severity, multiplicity, and etiology of pituitary deficiencies, leading to variable effects on body composition (1,9,14,30). In fact, insulin sensitivity was shown to be improved in AOGHD subjects compared with age-, sex-, and body mass index (BMI)-matched controls (28).…”

“…HUMANS WITH LONG-TERM adult-onset growth hormone deficiency (AOGHD) have been reported to have impaired glucose tolerance (5,27,32), systemic insulin resistance, and increased hepatic glucose production [HGP; (12,16,24)], with a higher prevalence of diabetes (1). However, the direct impact of growth hormone deficiency (GHD) on insulin-mediated glucose homeostasis is not clear cut.…”

Diabetes Mellitus in Neuroendocrine Diseases

“…Зависимость распространенности СД от уровня ИРФ-1, длитель-ности дефицита гормона роста, причины его разви-тия, наличия и количества недостаточности других гипофизарных гормонов не была установлена. Рас-пространенность СД у больных с дефицитом гормо-на роста до начала заместительной терапии состав-ляет 9,3% [41].…”