BackgroundIn type 2 diabetes mellitus both insulin resistance and hyperglycemia are considered responsible for autonomic dysfunction. The relation between the autonomic activity, impaired fasting glycemia and impaired glucose tolerance is, however, unclear. The purpose of this study was to evaluate and compare the circadian autonomic activity expressed as heart rate variability (HRV) measured by 24-hours ECG recording in insulin resistant subjects (IR) with characteristics as follow: IR subjects with normal oral glucose tolerance test results, IR subjects with impaired fasting glucose, IR subjects with impaired glucose tolerance and subjects with type 2 diabetes mellitus.MethodsEighty Caucasian insulin resistant subjects (IR) and twenty five control subjects were recruited for the study. IR subjects were divided into four groups according to the outcoming results of oral glucose tests (OGTTs): IR subjects with normal glucose regulation (NGR), IR subjects with impaired fasting glycemia (IFG), IR subjects with impaired glucose tolerance (IGT) and subjects with type 2 diabetes mellitus (DM). Autonomic nervous activity was studied by 24-hours ECG recording. Heart rate variability analysis was performed in time and frequency domains: SDNN, RMS-SD, low frequency (LF) and high frequency (HF) were calculated.ResultsThe total SDNN showed statistically significant reduction in all four groups with insulin resistant subjects (IR) when compared to the control group (p <0,001). During night LF normalized units (n.u.) were found to be higher in all four groups including IR subjects than in the control group (all p < 0,001) and subjects with normal glucose regulation (NGR), with impaired fasting glycemia (IFG) and with impaired glucose tolerance (IGT) were found to have higher LF n.u. than those in the type 2 diabetes mellitus group. The linear regression model demonstrated direct association between LF values and the homeostasis model assessment-index (HOMA-I), in the insulin resistant group (r = 0,715, p <0,0001).ConclusionThe results of our study suggest that insulin resistance might cause global autonomic dysfunction which increases along with worsening glucose metabolic impairment. The analysis of sympathetic and parasympathetic components and the sympathovagal balance demonstrated an association between insulin resistance and sympathetic over-activity, especially during night. The results indicated that the sympathetic over-activity is directly correlated to the grade of insulin resistance calculated according to the HOMA-I. Since increased sympathetic activity is related to major cardiovascular accidents, early diagnosis of all insulin resistant patients should be contemplated.

We studied the cases of 17 individuals who died suddenly of ventricular arrhythmia after prolonged use (median 5 months) of very low calorie weight reduction regimens consisting entirely or largely of protein. The deaths appeared to be independent of type of medical supervision received during the diet, daily dosage of potassium supplementation, and biological quality of the protein product used. Factors common to all cases were marked obesity at the onset of dieting, prolonged use of extremely low calorie diets (approximately 300 to 400 kcal daily), and significant and rapid weight loss. Our review of available electrocardiograms and pathological specimens revealed a pattern of cardiac changes previously described in starvation. We conclude that use of very low calorie weight reduction regimens should be curtailed until further studies determine what modifications, if any, can insure their safety.

Clinical and morphologic findings are described in 17 patients who died suddenly and unexpectedly during or shortly after use of the liquid-protein-modified-fast diet. Of the 17 patients, 16 were women, most were young (average age 37 years), and most lost a massive amount of weight (average 41 kg or 35% of their prediet weight) over a short period of time (average 5 months). Eight had one or more episodes of syncope. Multiple-lead ECGs were recorded in 10 patients. All had normal sinus rhythm; all had episodes of ventricular tachycardia; nine and possibly 10 patients had prolongation of the QT interval, unassociated with the recognized causes of QT interval prolongation in at least seven of the nine patients; and nine had diminished amplitude of the QRS complexes ("low voltage"). Histologic study of left ventricular myocardium in 14 patients disclosed attenuated myocardial fibers in 12, increased lipofuscin pigment in 11, and mononuclear-cell myocarditis in one. Similar histologic findings, however, also were found in 16 cachectic control subjects studied in similar fashion, but ECGs in them showed no prolongation of QT intervals or episodes of ventricular tachycardia. Thus, semistarvation, particularly in the face of antecedent obesity, is a cause of acquired QT interval prolongation, and repeated ECGs are recommended in patients on semistarvation diets for treatment of obesity. Observations in 17 patients and the role of the prolonged QT interval.Sudden, unexpected death in avid dieters using the liquid-protein-modified-fast diet.

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Patients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.