Hypoglycemia: A Possible Link between Insulin Resistance, Metabolic Dyslipidemia, and Heart and Kidney Disease (the Cardiorenal Syndrome)

Abstract

Resistance to insulin metabolic signaling in adipose tissue contributes to the lipid abnormalities in obese, hyperinsulinemic, insulin-resistant patients who develop the cardiorenal syndrome. These same metabolic dyslipidemic abnormalities can be found in conditions of caloric energy restriction with decreased adiposity or normal insulin levels, such as anorexia, starvation or non-diabetic kidney disease. In this review, we assess hypoglycemia as an alternative physiological explanation for the biochemical and lipid findings in conditions of insulin resistance (IR). Therefore, PubMed databases were searched for articles on the effect of hypoglycemia and starvation on non-esterified fatty acid (NEFA) elevation and abnormalities in insulin signaling in muscles as well as abnormal kidney metabolism. The search included articles on NEFA and their role in triglyceride (TG) and high-density lipoprotein (HDL) metabolism, as well as kidney and heart disease. Available studies support that hypoglycemia increases NEFA generation from adipose tissue. Elevated levels of NEFA induce increased plasma levels of TG and decreased levels of HDL cholesterol, and may cause direct kidney and myocardial damage. IR of adipose and skeletal muscle tissue, and the elevation in insulin levels in obese, insulin-resistant patients could be explained by an adaptation to their carbohydrate intake. These molecular abnormalities in insulin metabolic signaling can also be found in hypoglycemia or starvation. In conclusion, IR of adipose tissue cannot fully explain the lipid ab- normalities observed in the cardiorenal syndrome. Decreased blood glucose levels (e.g. hypoglycemia) occur frequently in patients at risk for this syndrome. Hypoglycemia-induced increases in NEFA levels can promote lipid abnormalities that contribute to IR and the cardiorenal syndrome.

Metabolic Parameters in Patients with Suspected Reactive Hypoglycemia

“…Therefore, hyperinsulinemia and insulin resistance do not necessarily have to be responsible for the occurrence of hypoglycemia. However, there are studies with HR patients who had insulin resistance and significant impairment of insulin secretion [ 31 , 32 ]. Due to discrepancies in the findings of the studies and considering the lack of up-to-date evidence from other publications, further research focusing on insulin secretion and insulin sensitivity in RH patients is required.…”

Insulin resistance and obesity, and their association with depression in relatively young people: findings from a large UK birth cohort

“…In addition, more sensitive markers of pre-clinical glucose dysregulation (FI, HOMA 2 ) were positively associated with depression at age 18 years. IR in combination with low FPG shows biological plausibility; FPG can present low-normal in early IR, in response to the IR phenotype of increased insulin secretion thus increased intracellular glucose uptake (Ensling et al ., 2011). These associations were not significant following demographic and lifestyle adjustments suggesting that the metabolic dysfunction present in depression may be attributable to sociodemographic and lifestyle factors.…”

Association of Hypoglycemia With Incident Chronic Kidney Disease in Patients With Type 2 Diabetes

“…Although the exact mechanism is not well understood, a preclinical study demonstrated that hypoglycemia can induce nonesterified fatty acid elevation in adipose tissue, which is subsequently associated with kidney damage. 35 In addition, hypoglycemia could induce sympathetic surges, altering renal hemodynamics 10 ; acute fluctuations in blood glucose levels also trigger oxidative stress, which may be responsible for renal function impairment. 9 …”