Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60

Despite more than 80 years of intensive and outstanding research, it remains to be determined how Type 2 (non-insulin dependent) Diabetes (T2D) results in extensive angiopathy and elevated Pulse Pressure (PP) in patients over 60 years of age, with large risks for heart attack or stroke. We present below a summary of recent findings from our laboratories which may give us clues to a better understanding of these very dangerous pathologies. Our studies present cogent reasons for why T2D is a multivariate syndrome with numerous pitfalls. T2D appears to be due, in origin, to numerous pathological pathways working in concert which lead to elevated PP (in the elderly), heart failure and/or stroke. Our observations on isolated animal tissues and cells as well as T2D subjects support a major role for Mg deficiency as a prime trigger leading to the production and release of ceramides (and possibly other sphingolipids), certain phospholipids (i.e., PKC isozymes), membrane peroxidation, activation of NADPH oxidase, Platelet-Activating Factor (PAF), reactive oxygen and nitrogen species, and release/generation of cytokines and adhesion molecules, all of which can be ameliorated by increased dietary intake and supplemental Mg. Based on extensive biochemical and biophysical-molecular assays, performed in our labs (reviewed herein), we are convinced that long-term Mg deficiency produces genotoxic effects which cause epigenetic alterations (e.g., angiogenetic/atherogenic) in cell phenotypes resulting in micro- and microvascular changes in T2D patients.