Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance

Summary We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants. Learning points Insulin receptor (INSR) gene variants can be a cause of monogenic diabetes in children and adolescents. Genetic evaluation should be considered in children and adolescents with type 2 diabetes (T2D), particularly where there is an atypical presentation and/or positive family history. Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.

Effect of a multitarget therapy with prednisolone, mycophenolate mofetil, and tacrolimus in a patient with type B insulin resistance syndrome complicated by lupus nephritis

ABSTRACT Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease characterised by autoantibodies targeting insulin receptors. TBIR is often complicated by systemic lupus erythematosus (SLE). We describe the case of a 59-year-old Japanese man with TBIR complicated with lupus nephritis (LN), who presented with nephrotic syndrome and severe hypoglycaemia. Treatment with prednisolone (PSL), mycophenolate mofetil (MMF), and tacrolimus (TAC) resulted in improved SLE activity and glucose intolerance with the reduction of anti-insulin receptor autoantibodies. To the best of our knowledge, this is the first reported case of TBIR complicated with LN that was successfully treated using multitarget therapy with PSL, MMF, and TAC.

Lipid behavior in metabolic syndrome pathophysiology

: Undeniably, lipid plays an extremely important role in the homeostasis balance, since lipid contributes to the regulation of the metabolic processes. The metabolic syndrome pathogenesis is multi-pathway that composes neurohormonal disorders, endothelial cell dysfunction, metabolic disturbance, genetic predisposition, in addition to gut commensal microbiota. The heterogenicity of the possible mechanisms gives the metabolic syndrome its complexity and limitation of therapeutic accesses. The main pathological link that lipid contributes to the emergence of metabolic syndrome via central obesity and visceral obesity that consequently lead to oxidative stress and chronic inflammatory response promotion. Physiologically, a balance is kept between the adiponectin and adipokines level to maintain the lipid level in the organism. Clinically, extremely important to define the borders of the lipid level in which the pathogenesis of the metabolic syndrome is reversible, otherwise will be accompanied by irreversible complications and sequelae of the metabolic syndrome (cardiovascular, insulin resistance). The present paper is dedicated to providing novel insights into the role of lipid in the development of metabolic syndrome hence dyslipidemia is the initiator of insulin resistance syndrome (metabolic syndrome).

Calcium-Deficiency during Pregnancy Affects Insulin Resistance in Offspring

Prenatal malnutrition is known to affect the phenotype of the offspring through changes in epigenetic regulation. Growing evidence suggests that epigenetics is one of the mechanisms by which nutrients and minerals affect metabolic traits. Although the perinatal period is the time of highest phenotypic plasticity, which contributes largely to developmental programming, there is evidence of nutritional influence on epigenetic regulation during adulthood. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. Cortisol, the most important glucocorticoid, is considered to lead to insulin resistance and metabolic syndrome. 11β-hydroxysteroid dehydrogenase-1 is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. This brief review aims to identify the effects of Ca deficiency during pregnancy and/or lactation on insulin resistance in the offspring. Those findings demonstrate that maternal Ca deficiency during pregnancy may affect the epigenetic regulation of gene expression and thereby induce different metabolic phenotypes. We aim to address the need for Ca during pregnancy and propose the scaling-up of clinical and public health approaches that improved pregnancy outcomes.

A comparative study of metabolic profile in pre-eclampsia and normotensive preterm pregnancy

Background: Hypertensive disorders of pregnancy are important and common cause of severe acute morbidity, long-term disability and death among mothers and babies. The metabolic characteristics (hypertriglyceridemia, hyperinsulinemia, hyperuricemia, low HDL2 cholesterol) in pregnancy-induced hypertension resemble the main features of the “insulin resistance syndrome”. This may result in endothelial cell dysfunction as evidenced by PGI2 suppression. We have designed this study with an objective to compare the metabolic parameters like fasting and post prandial blood glucose, fasting plasma insulin, HOMA-IR and lipid profile between pre-eclampsia and normotensive pregnant women at late preterm (32-36 weeks).Methods: Based on enrolment criteria and statistical analysis 224 patients were enrolled in study during study period and divided in to two groups, group 1- normotensive subjects, group2- pre-eclampsia subjects. Various biochemical parameters and obstetric profile was measured and compared with standard normotensive subjects.Results: The mean fasting plasma insulin was significant higher in group 2 than group 1 (18.36±6.48 mIU/dl versus 3.42±1.68 mIU/dl) (p=0.0001). The mean value of HOMA-IR was significant higher in group 2 than group 1 (3.82±1.68 versus 1.98±1.68) (p=0.0001). The mean value of HDL was significant higher in group 1 than group 2 (42.56±3.28 mg/dl versus 34.26±3.63 mg/dl) (p=0.0001). The mean concentration of LDL was significant higher in group 2 than group 1 (142.23±24.36 mg/dl vrsus 84.32±18.24 mg/dl) (p=0.0001).Conclusions: Systolic and diastolic blood pressure was significantly higher in preeclampsia patients and plasma fasting glucose was higher in normotensive subjects. In present study fasting plasma insulin and HOMA-IR are significantly higher in cases then control. Dyslipidemia is significantly evident in preeclampsia patients in our study.