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Aging is epidemiologically linked to an increased incidence of hypertension, impaired glucose tolerance and overt non-insulin dependent diabetes mellitus type II (NIDDM). The cellular basis underlying this clinical and epidemiological linkage, cytosolic free calcium (Ca(2+)(i)) and cytosolic free magnesium (Mg(2+)(i)) levels were investigated in elderly subjects and in subjects with essential hypertension (EH) and metabolic diseases. It has been observed that normal aging, as well as hypertension and NIDDM, is characterized by elevated Ca(2+)(i) and suppressed Mg(2+)(i) levels. Furthermore, the divalent ionic defect displayed in EH and NIDDM resembled the normal aging process, i.e., ionic levels in both young and elderly subjects with EH or NIDDM were indistinguishable from those in healthy elderly subjects. The ionic levels predict quantitatively also the extent of elevated blood pressure, and hyperinsulinemic response to oral glucose challenge. Altogether, we suggest that the missing link, responsible for the frequent and increasing clinical coexistence of hypertension, insulin resistance, impaired glucose tolerance, and NIDDM with age, may be ionic in nature, and intrinsic to the normal aging process in Western man.

Several studies have shown that centenarians have better cardiovascular risk profiles compared to younger old people. Some reports have revealed that cardiovascular diseases (i.e. hypertension, diabetes, angina and/or myocardial infarction) are less common in centenarians respect to 70 and 80 years old persons. In order to explain this evidence, there is a growing number of hypothesis that consider a combination of genetic factors and lifestyle aspects to elucidate the exceptional longevity of centenarians, able to overcome the most frequent mortality cause, which is a cardiovascular event. It has been suggested that a role on this better cardiovascular risk profile may be played by the increasing use of pharmacologic treatments in the elderly population (specially for hypertension and dyslipidemia), but the contribution of drug treatments to promote extreme longevity is not confirmed. Furthermore, centenarians in general have needed fewer drugs at younger ages due to a healthy lifestyle. The importance of the genetic contribution is demonstrated by the inheritance of low-risk cardiovascular profiles in centenarian offspring and lower prevalence of cardiovascular diseases in this population as compared with their spouses or with age-matched subjects without centenarian parents. Another advantage in centenarians' offspring seems to be a delay in the onset for cardiovascular diseases, respect to age- and sex-matched controls. Cardiovascular risk factors mirror the factors that contribute to longevity. Hence, it is not surprising that these risk factors are less prevalent in centenarians when compared to younger old individuals.

Diabetic neuropathy is a common chronic complication of diabetes and cause of significant morbidity and mortality, because it may involve the autonomous and peripheral nervous systems. Autonomic diabetic neuropathy is a challenging chronic complication of long-standing diabetes manifested with hypotension, syncope, gastroparesis, diarrhea, constipation, bladder dysfunction, sexual dysfunction, cardiac arrest, and/or sudden death. We present a case of diabetic gastroparesis in an older woman. The patient was an 83-year-old woman with a 40-year history of type 2 diabetes who was admitted with hypoglycemia, malnutrition, persistent vomiting, and obstinate constipation. After several unsuccessful attempts with different therapies, we administered intravenous azithromycin (500 mg/day). After 3 days of treatment, vomiting was resolved and the patient evacuated normal feces, with notable improvement in the general conditions and metabolic control. Because diabetic gastroparesis frequently is difficult to manage clinically and there are few beneficial therapeutic choices available at present, the macrolide antibiotic azithromycin, which has strong prokinetic properties, may be a useful option in the treatment of this complex condition.

Magnesium plays a key role in regulating insulin action, insulin-mediated glucose uptake, and vascular tone. Intracellular magnesium depletion may result in a defective tyrosine—kinase activity at the insulin receptor level, in a postreceptorial impairment in insulin action, and clinically in a worsening of insulin resistance. Intra- and extracellular alterations of magnesium metabolism have been identified in clinical states characterized by insulin resistance, such as metabolic syndrome, hypertension, altered glucose tolerance, type 2 diabetes, and aging. Several studies, from our and other’s groups, have confi rmed the clinical relevance of alterations of magnesium homeostasis in these conditions and have highlighted the importance of an accurate definition of the magnesium status. While measurements of total serum magnesium levels have been proven inadequate for this purpose because important magnesium depletions are required before total serum level decreases, two technologies, 31P nuclear magnetic resonance (31P-NMR) spectroscopy and magnesium-specifi c ion-selective electrodes, that, respectively, measure intracellular and extracellular free levels of magnesium, have a higher sensitivity in detecting magnesium deficits. A number of evidences have confirmed that magnesium supplementation is indicated in conditions associated with magnesium deficit, although well-designed therapeutic trials with oral magnesium supplements to study the beneficial effects in metabolic syndrome and in type 2 diabetes are needed.

OBJECTIVES: Hyperhomocysteinemia and oxidative stress are independent risk factors for cardiovascular events, which occur more frequently in old age. We evaluated these parameters in relation to age and the presence of hypertension and type 2 diabetes mellitus. METHODS: Two hundred eighty-two subjects (female/male: 142/140; 141 were >65 years and 141 were