Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels

Fibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise.This was a comparative longitudinal study. Anthropometric and biochemical evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m². The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8-568.6) vs. (460.8 (298.2-742.1), p<0.0001)). The delta (final-basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r² = 0.64, p<0.0001).Serum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise.ClinicalTrials.gov NCT01512368

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Metabolic syndrome and non-alcoholic fatty liver disease

The development of nonalcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome as reflected by the fact that approximately 90% of the patients with NAFLD have more than one feature of metabolic syndrome and about 33% have three or more criteria. The physiopathology, epidemiology and therapeutic considerations of the disease are reviewed here. Lipotoxicity plays a predominant role in the pathophysiology of both entities. It leads to accumulation of triglycerides in the liver as a result of an imbalance among the uptake, synthesis, export, and oxidation of fatty acids. Both conditions are very common in Mexico. Using the Adult Treatment Panel diagnostic criteria, the 1994 prevalence of the metabolic syndrome was 26.6%.Although the prevalence of NAFLD is not known, but it can be estimated from the prevalence of obesity (30%). Since NAFLD is found in over two thirds of the obese subjects, this condition may exist in 20% of the adult population. The treatment of both conditions should be based in an integral approach, including the adoption of a healthy lifestyle, weight loss and may be pharmacotherapy. In summary, NAFLD is the hepatic expression of the metabolic syndrome. The study and treatment of these disorders could not be viewed as separate issues

Metabolic syndrome and non-alcoholic fatty liver disease.

Abstract The development of nonalcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome as reflected by the fact that approximately 90% of the patients with NAFLD have more than one feature of metabolic syndrome and about 33% have three or more criteria. The physiopathology, epidemiology and therapeutic considerations of the disease are reviewed here. Lipotoxicity plays a predominant role in the pathophysiology of both entities. It leads to accumulation of triglycerides in the liver as a result of an imbalance among the uptake, synthesis, export, and oxidation of fatty acids. Both conditions are very common in Mexico. Using the Adult Treatment Panel diagnostic criteria, the 1994 prevalence of the metabolic syndrome was 26.6%.Although the prevalence of NAFLD is not known, but it can be estimated from the prevalence of obesity (30%). Since NAFLD is found in over two thirds of the obese subjects, this condition may exist in 20% of the adult population. The treatment of both conditions should be based in an integral approach, including the adoption of a healthy lifestyle, weight loss and may be pharmacotherapy. In summary, NAFLD is the hepatic expression of the metabolic syndrome. The study and treatment of these disorders could not be viewed as separate issues. Key words: Non alcoholic fatty liver disease, metabolic syndrome, hepatic esteatosis, insulin resistance, tryglicerides. The metabolic syndrome is a condition characterized by a cluster of alterations including glucose intolerance/ insulin resistance, abdominal obesity, atherogenic dyslipidemia (low concentrations of high-density lipoprotein-cholesterol and high concentrations of triglycerides), elevated blood pressure, a proinflammatory and a prothrombotic state. It increases morbidity and mortality, especially due to cardiovascular disease. 1,2 On table I the diagnostic criteria for the syndrome according to different organizations are shown. According to some groups, insulin resistance is the main feature of the metabolic syndrome. Insulin resistance refers to a condition in which a greater amount of insulin are required to elicit a normal biologic response at a cellular, organ or whole-body level. As insulin resistance increases, a greater degree of compensatory hyperinsulinemia is present. 1,3 In Mexico there is a high prevalence of the metabolic syndrome. Using the Adult Treatment Panel (ATP III) diagnostic criteria, a prevalence of 26.6% was estimated and according to the WHO criteria the prevalence was 13.61%. A significant proportion of the total cases (35.2%) are less than 40 years of age and in people without diabetes the age distribution is shifted to a younger group regardless the diagnostic criteria used. The metabolic syndrome was more common in women than in men (13.39% vs 13.79%) according to the WHO criteria and more common in men (28.5% vs 25.2%) according to the ATP III. The number of cases was significantly lower with the WHO definition; in fact only 43.4% of the subjects who fulfilled the ATP III criteria were diagnosed using the WHO definition

Atypical Parathyroid Adenoma Complicated with Protracted Hungry Bone Syndrome after Surgery: A Case Report and Literature Review

Hungry Bone Syndrome refers to the severe and prolonged hypocalcemia and hypophosphatemia, following parathyroidectomy in patients with hyperparathyroidism. We present the case of an eighteen-year-old woman with a four-year history of hyporexia, polydipsia, weight loss, growth retardation, and poor academic performance. The diagnostic work-up demonstrated primary hyperparathyroidism with hypercalcemia of 13.36 mg/dL, a PTH level of 2551 pg/mL, bone brown tumors, and microcalcifications within pancreas and kidneys. Neck ultrasonography revealed a parathyroid adenoma of 33 × 14 × 14 mm, also identified on 99Tc-sestamibi scan. Bone densitometry showed decreased Z-Score values (total lumbar Z-Score of −4.2). A right hemithyroidectomy and right lower parathyroidectomy were performed. Pathological examination showed an atypical parathyroid adenoma, of 3.8 g of weight and 2.8 cm in diameter. After surgery she developed hypocalcemia with tetany and QTc interval prolongation. The patient required 3 months of oral and intravenous calcium supplementation due to Hungry Bone Syndrome (HBS). After 42 months, she is still under oral calcium. Usually HBS lasts less than 12 months. Therefore we propose the term “Protracted HBS” in patients with particularly long recovery of 1 year. We present a literature review of the diagnosis, pathophysiology, and treatment of HBS