Abstract
BackgroundOverweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear.AimTo evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism.MethodsPatients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks.ResultsTwenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment.ConclusionsThis is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.
Highlights
Overweight and obesity are characterized by an excess of fat-mass accumulation
The reduction of sex hormone-binding globulin (SHBG) serum levels, the increased androgen aromatization into estrogens, and the pro-inflammatory cytokine-dependent attenuation of luteinizing hormone (LH) pulses [2] represent some of the mechanisms explaining the occurrence of male hypogonadism in overweight and obesity [3]
Eighteen patients were excluded for low compliance to the Very low-calorie ketogenic diet (VLCKD) protocol (n = 8) and recurrent fever (n = 2)
Summary
Overweight and obesity are characterized by an excess of fat-mass accumulation. They represent two widely spread conditions, whose prevalence doubled since the 1980s, currently affecting one-third of the global population [1]. There is a tight connection between obesity and the development of comorbidities such as type 2 diabetes mellitus (T2DM), dyslipidemia, cerebrovascular and cardiovascular disease, arthrosis, psychiatric disorders, obstructive sleep apnea, cholelithiasis, and non-alcoholic fatty liver disease. It heavily affects the quality of life and severely burdens the healthcare. Aim To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism
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