Arshag D. Mooradian

Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association.

Medical nutrition therapy (MNT) is important in preventing diabetes, managing existing diabetes, and preventing, or at least slowing, the rate of development of diabetes complications. It is, therefore, important at all levels of diabetes prevention. MNT is also an integral component of diabetes self-management education (or training). This position statement provides evidence-based recommendations and interventions for diabetes MNT. The previous position statement with accompanying technical review was published in 2002 and modified slightly in 2004. This statement updates previous position statements, focuses on key references published since the year 2000, and uses grading according to the level of evidence available...

Effect of Protein Ingestion on the Glucose and Insulin Response to a Standardized Oral Glucose Load

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 ± 35, 83 ± 19 µU · h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 ± 33 µU · h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.

Effect of aging on the blood-brain barrier

Aging is commonly associated with progressive deterioration in central nervous system (CNS) function. Nutritional factors or environmental toxins have important effects on CNS degenerative changes. The blood-brain barrier (BBB) is a major modulator of nutrient delivery to the CNS. The tight junctions and the paucity of pinocytosis or fenestrations in brain capillary endothelium act as an effective barrier between the CNS and the circulating toxic agents. Senescence is associated with significant, though often subtle, changes in BBB. Conditions which are commonly associated with aging, such as hypertension and cerebrovascular ischemia, aggravate the age-related alterations in BBB function. The histologic changes in brain vasculature with aging is region selective and species specific. The common age-related histologic changes include loss of capillary endothelial cells, elongation of the remaining endothelial cells, and decreased capillary diameter in rat cortex, but not in the monkey or human cortex, and a decrease in the number of mitochondria in endothelial cells of the brain capillaries in the monkey but not in the rat. The age-related alterations in BBB transport function include a decrease in BBB choline transport with aging and decreased brain glucose influx. The BBB neutral amino acid transport appears to be unaltered in the aged mice. Most of the studies reported so far have failed to show a significant age-related alteration in BBB permeability to water-soluble substances and high molecular weight solutes in the absence of neurological disease. A more profound change in BBB permeability appears to be associated with Alzheimers disease. Immunohistological studies have demonstrated the presence of serum proteins in the cerebrovascular amyloid in patients with Alzheimers disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Impotence and Aging: Clinical and Hormonal Factors

A cross‐sectional study of 216 impotent men aged 40 to 79 years (mean age 60.9 years) was conducted to determine if there are age‐related changes in clinical and hormonal parameters in an impotent population. There was a slight increase in the degree of sexual dysfunction with age, with complete erectile failure occurring in a larger percent of the 60‐ and 70‐year‐olds than in the younger patients (41% vs 27% for the 40 year olds, P < .05). No patient above the age of 70 years reported any full erections, even of short duration. In contrast, reported levels of libido did not vary significantly with age. Abnormal penile Doppler studies diagnostic of vasculogenic impotence were found in 17.8% of the patients tested, and an additional 17.8% were found to have evidence suggestive of a vascular etiology. These abnormal vascular findings were associated with an extremely high prevalence of clinically apparent atherosclerosis in this population. In 22.9% of the subjects, an abnormal vascular response was found only on exercise, ie, a “pelvic steal”, which only occurred above the age of 50 years. There was a marked age‐related alteration in the concentration of testosterone CD and bioavailable testosterone (BT), but no statistically significant change in the levels of gonadotropins with age. An increase in the prevalence of eugonadotropic hypogonadism with age was found, which suggested an increasing prevalence of hypothalamic pituitary dysfunction in this patient group. For both vascular and hormonal changes (such as low T and BT), the greatest changes appear to occur after the age of 50.

Mechanism of pain in diabetic peripheral neuropathy: Effect of glucose on pain perception in humans

Animal studies have suggested an altered response to opiate agonists and antagonists as well as an altered pain threshold in diabetic animals. In the studies reported herein, a 50 g glucose infusion in normal subjects resulted in a significant decrease in both the threshold level of pain and the maximal level of pain tolerated, as measured by responses to electrical pain induced by a Grass stimulator. In addition, patients with diabetes mellitus were hyperalgesic when compared with normal subjects. It is concluded that elevated glucose levels and/or rapid fluxes in glucose levels result in a decrease in pain tolerance. These findings have potential clinical implications in the pathophysiology and management of painful diabetic neuropathy and the use of narcotic agents in diabetes mellitus.

The relationship between muscle mass and muscle strength in the elderly.

To determine the extent that muscle mass is predictive of muscle strength in the elderly, anthropomorphic estimates of muscle area and impedance measurements of muscle mass and peak isometric muscle strength were obtained in a relatively healthy older population over 65 years of age (mean age = 71.7; n = 218). Midarm muscle area correlated strongly with upper arm strength (r = 0.68, P < 0.0001) while midthigh muscle area had a much lower correlation with thigh muscle strength (r = 0.29, P < 0.0001). These muscle area calculations also include bone area. Lean body mass calculated by bioelectric impedance correlated highly with cumulative muscle strength measured by summing all muscle groups (r = 0.79, P < 0.0001). To determine whether aging alters muscle strength per unit of muscle mass, additional middle‐aged subjects were included, and three groups, middle‐aged (55–64) (n = 78), young‐old (65–74) (n = 161), and old‐old (75+) (n = 57), were compared. A significant age‐related trend of decreasing muscle strength per unit of lean body mass was noted. It is concluded that although muscle mass correlates with muscle strength in a healthy older population, use of simple age‐independent clinical measurements of body mass should not be used to predict muscle strength.

Design and Baseline Characteristics for the Aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTION II)

Advanced glycosylation endproduct (AGE) formation has been implicated in the development and progression of nephropathy in type 2 diabetes mellitus. In diabetic animals, aminoguanidine inhibits AGE-mediated cross-linking of proteins in vascular and renal tissue and slows the progression of renal disease. ACTION II is a randomized, double-blind, placebo-controlled trial comparing two dose levels of aminoguanidine with placebo on the progression of nephropathy in 599 type 2 diabetic patients with renal disease from 84 centers in the United States and Canada. The primary endpoint is time to doubling of serum creatinine concentration. Secondary endpoints include the effect of aminoguanidine on time to all-cause mortality, end-stage renal disease (ESRD), cardiovascular morbidity and mortality, rate of change in indices of renal function (iothalamate, Cockcroft and Gault [C&G] calculated creatinine and measured creatinine clearances), proteinuria, retinopathy, circulating and urinary AGE levels, and estimation of the relationship between plasma aminoguanidine concentrations and primary and secondary efficacy endpoints and adverse events. Progression of macrovascular disease was monitored and fundus photography performed. Type 2 diabetic patients aged 30 to 70 years were eligible for the trial if their blood pressure was < or =180 mm Hg systolic and < or =120 mm Hg diastolic, serum creatinine concentration > or =1.0 mg/dL (in women) or > or =1.2 mg/dL (in men), C&G clearance > or =40 mL/min, and proteinuria > or =500 mg/d with diabetic retinopathy or diabetic nephropathy on renal biopsy. Recruitment began in July 1995 and terminated in December 1996. The trial randomized a total of 599 subjects. At baseline, the mean (standard deviation [SD]) age was 58 (7.7) years, diabetes duration 16.5 (7.5) years, body mass index 32 kg/m2 (10-90% range 2642), arterial blood pressure 105 (12) mm Hg, C-peptide concentration 2.55 (1.71) ng/mL, serum glucose concentration 201 (89) mg/dL, hemoglobin A1c 8.7% (1.6), serum creatinine concentration 1.6 (0.5) mg/dL, iothalamate clearance 52 (25) mL/min/1.73 m2, proteinuria 4.1 (4.2) g/d, triglycerides 259 (214) mg/dL, and LDL cholesterol 144 (40) mg/dL. Patients are 72% male, 68% white, 16% black, and 16% Asian American and Native American. At baseline, 76% were receiving concomitant angiotensin-converting enzyme (ACE) inhibitors and 43% lipid-lowering agents. Follow-up in ACTION II was scheduled to continue through December 1998, so that follow-up was to be 2 years after the date of randomization of the final enrolled patient. The trial in fact ended in March 1998. This trial will contribute to our understanding of the natural history of type 2 diabetes mellitus-associated nephropathy and determine whether aminoguanidine will slow the progression of established diabetic renal disease.

Characteristics of Learning and Memory in Streptozocin-Induced Diabetic Mice

We demonstrated that mice with streptozocin-induced diabetes mellitus have normal acquisition for relatively simple tasks but show problems in learning more complex tasks such as shuttle box avoidance. Enhanced learning previously reported in simple passive avoidance tasks appears to be due to increased foot shock sensitivity. Diabetic mice show a marked memory retention deficit after learning an active avoidance T-maze task. This retention deficit was reversed by a single injection of insulin, suggesting that it may be related to hyperglycemia per se. Diabetic mice have a shift to the left in the inverted U-shaped dose-response curve for memory retention produced by the acetylcholine agonist arecoline. Based on a preliminary screening, responses to several other pharmacological memory enhancers are probably altered in diabetic mice. These studies suggest that this mouse model of diabetes mellitus demonstrates a deficit in memory retention and retrieval similar to that seen in humans with diabetes mellitus.

Selected Vitamins and Minerals in Diabetes

The interrelationship between diabetes and various vitamins and minerals is characterized by a high degree of reciprocity. Chronic uncontrolled hyperglycemia can cause significant alterations in the status of these nutrients, and conversely, some of these substances, especially those that have been characterized as micronutrients, can directly modulate glucose homeostasis (1). Differences in patient populations studied and methodological uncertainties account for the discrepancies in most reported studies. Certain subgroups of individuals with diabetes, such as elderly patients, vegans (who consume no animal products), and pregnant and lactating women, are at particular risk for deficiencies for such nutrients. Additionally, caloric restriction for obese patients and the effects of a high fiber diet and a host of drugs on the metabolism of vitamins and minerals are of concern (2,3).

American diabetes association position statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications

Medical nutrition therapy for people with diabetes should be individualized, with consideration given to the individuals usual food and eating habits, metabolic profile, treatment goals and desired outcomes. Monitoring of metabolic parameters, including glucose, HbA1c, lipids, blood pressure, body weight, and renal function, when appropriate, as well as quality of life is essential to assess the need for changes in therapy and ensure successful outcomes. Ongoing nutrition self-management education and care needs to be available for individuals with diabetes. Additionally many areas of nutrition and diabetes require additional research.