Effects of growth hormone on hepatic insulin sensitivity and glucose effectiveness in healthy older adults

Forrest, Lala L.; Sedmak, Caroline; Sikder, Shanaz; Grewal, Shivraj; Harman, S. Mitchell; Blackman, Marc R.; Muniyappa, Ranganath

doi:10.1007/s12020-018-01834-4

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…Patients with acromegaly have an increased glucose turnover, as GH increases hepatic glucose production by increasing glycogenolysis (17). Chronic GH administration impairs insulin sensitivity in the liver, thereby reducing the ability of insulin to suppress gluconeogenesis and glucose output (12, 32, 61).…”

Section: Pathophysiology Of Insulin Resistance In Acromegalymentioning

confidence: 99%

Insulin Resistance in Patients With Acromegaly

et al. 2019

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Acromegaly is characterized by chronic overproduction of growth hormone (GH) that leads to insulin resistance, glucose intolerance and, ultimately, diabetes. The GH-induced sustained stimulation of lipolysis plays a major role not only in the development of insulin resistance and prediabetes/diabetes, but also in the reduction of lipid accumulation, making acromegaly a unique case of severe insulin resistance in the presence of reduced body fat. In the present review, we elucidate the effects of GH hypersecretion on metabolic organs, describing the pathophysiology of impaired glucose tolerance in acromegaly, as well as the impact of acromegaly-specific therapies on glucose metabolism. In addition, we highlight the role of insulin resistance in the development of acromegaly-associated complications such as hypertension, cardiac disease, sleep apnea, polycystic ovaries, bone disease, and cancer. Taken together, insulin resistance is an important metabolic hallmark of acromegaly, which is strongly related to disease activity, the development of comorbidities, and might even impact the response to drugs used in the treatment of acromegaly.

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Section: Pathophysiology Of Insulin Resistance In Acromegalymentioning

confidence: 99%

Insulin Resistance in Patients With Acromegaly

et al. 2019

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“…Moreover, the mechanisms promoting increasing concentrations of SHBG with advancing age is yet to be elucidated, however, a plausible theory exists (Figure 4). Since growth hormone (GH) induces hepatic IR (Forrest et al, 2019; Mercado & Ramirez‐Renteria, 2018), resulting in reduced SHBG synthesis, a reduction in GH concentrations due to aging (Chahal & Drake, 2007) may improve hepatic insulin sensitivity and therefore, increase SHBG synthesis (Thaler et al, 2015). Hence, the gradual increase in SHBG concentrations in men as they age.…”

Section: Discussionmentioning

confidence: 99%

Examining the associations between testosterone and biomarkers as men age

Smith

Bekele

Lopresti

et al. 2023

American J Hum Biol

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ObjectivesTestosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone‐binding globulin (SHBG), using a large nationally‐representative data set (National Health and Nutrition Examination Survey; NHANES).MethodsNHANES is a cross‐sectional survey, physical examination, and laboratory evaluation of a nationally‐representative sample of a non‐institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013–2014 and NHANES 2015–2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA‐IR), insulin, glucose, and age.ResultsAn overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA‐IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA‐IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre‐diabetic HOMA‐IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables.ConclusionThe results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

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“…However, some have reported that GH treatment reduced insulin sensitivity [ 24 ]. In healthy older subjects, GH administration for 26 weeks impaired insulin sensitivity in the liver, but not in skeletal muscle [ 25 ]. Although we considered that the development of type 2 diabetes was not caused by GH treatment in this case, because no abnormal blood glucose levels were found during the GH treatment and six years had already passed after the end of the treatment, long-term GH treatment might have been involved in the pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Non-Obese Type 2 Diabetes with a History of Being an Extremely Preterm Small-for-Gestational-Age Infant without Early Adiposity Rebound

Nagano

Kaneko

Seya

et al. 2022

IJERPH

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Adiposity rebound (AR), which is defined as a situation in which the body mass index (BMI) starts to increase after infancy, is a predictive marker of future development of type 2 diabetes. The patient was a 20-year-old male. He was born at 28 gestational weeks with a birthweight of 642 g (−3.20 standard deviation, small-for-gestational age [SGA]). AR during early childhood or obesity in later childhood was not observed. At the onset of type 2 diabetes (20 years of age), his BMI, body fat percentage, and body fat mass were within normal ranges (20.4, 18.4% and 10.8 kg, respectively). However, his muscle mass was 44.7 kg, with low muscle mass of the trunk and upper limbs, which was lower than the standard reference, indicating that myogenic insulin resistance was involved in the development of non-obese type 2 diabetes. This case report describes a patient with no presentation of AR and obesity during childhood, who was born extremely preterm SGA, developed non-obese type 2 diabetes with low muscle mass. We suggest that patients born extremely preterm SGA should be carefully observed for the development of type 2 diabetes, even if they did not have AR in early childhood or had not become obese.

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Effects of growth hormone on hepatic insulin sensitivity and glucose effectiveness in healthy older adults

Cited by 8 publications

References 55 publications

Insulin Resistance in Patients With Acromegaly

Insulin Resistance in Patients With Acromegaly

Examining the associations between testosterone and biomarkers as men age

Non-Obese Type 2 Diabetes with a History of Being an Extremely Preterm Small-for-Gestational-Age Infant without Early Adiposity Rebound

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