A biethnic community survey of cognition in participants with type 2 diabetes, impaired glucose tolerance, and normal glucose tolerance: the New Mexico Elder Health Survey.

OBJECTIVE: To determine whether elderly individuals with type 2 diabetes or impaired glucose tolerance are at increased risk for cognitive impairment compared with individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: Elderly Hispanic individuals (n = 414) and non-Hispanic white individuals (n = 469) aged > or =65 years, randomly selected from the Medicare rolls of Bernalillo County (Albuquerque), NM, were recruited for an interview/examination that included an evaluation of glucose tolerance. Information on nine tests of cognitive function and two measures of depression allowed comparisons between diabetic status and these functions. Comparisons also were made between glycosolated hemoglobin concentrations and these cognitive tests in the 188 participants with diabetes. RESULTS: None of the mean scores on the tests of cognitive function was significantly lower in the participants with diabetes compared with those participants with normal glucose tolerance after adjustments for ethnicity, sex, age, level of education, and presence of depression, with or without elimination of those with dementia (Mini-Mental State Exam <18). Interestingly, participants with impaired glucose tolerance tended to score higher than those with normal glucose tolerance. No significant associations were found between glycosolated hemoglobin concentrations and cognitive test scores in participants with diabetes. CONCLUSIONS: We could not show any increased risk for cognitive impairment in participants with diabetes compared with those with normal glucose tolerance after adjustments for ethnicity, sex, age, education, and presence of depression, before or after elimination of dementia in this random sample from a biethnic population of predominantly community-dwelling elders.

Prevalences of type 2 diabetes, the insulin resistance syndrome, and coronary heart disease in an elderly, biethnic population.

OBJECTIVE: To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites. RESEARCH DESIGN AND METHODS: Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age > or = 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD. RESULTS: Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups. CONCLUSIONS: Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.

Effect of estrogen-progestogen administration on tissue cation concentrations in the rat.

Five studies are reported which were designed to define the effects of an estrogen and a progestogen, alone and in combination, on tissue concentrations (heart, kidney, and liver) of two trace metals (zinc, copper) and four bulk cations (sodium, potassium, calcium, magnesium). Male rats received Premarin (0.08 mg) and/or progesterone (2 mg) in saline intramuscularly 5 days a week for 12 weeks. A significant increase in kidney copper concentrations was the most striking finding in treated, compared to control, animals. A small but significant increase in kidney zinc concentrations also was observed. The changes in cation concentrations in the liver were less striking and consistent, and no changes were observed in cation concentrations of heart muscle. The increase in renal copper was greater with estrogen than with progestogen alone but the two in combination produced an additive effect. Dose-response and time-response changes were documented. Two weeks after discontinuing treatment, renal copper and zinc concentrations returned to control levels.

A specific dietary zinc requirement for the growth of Walker 256/M1 tumor in the rat.

To determine the specific effect of zinc status on the growth of Walker 256/M1 carcinosarcomas young male rats were pair-fed either a control or zinc-deficient diet for 14 days, were implanted with tumors and killed 7 days later. Half of the deficient rats were repleted with zinc for the 7 days after tumor implantation. In deficient rats, tumor weights were decreased 70% (p less than 0.005), tumor necrosis was 3-fold greater (p less than 0.05) and tumor zinc concentrations were decreased 23 to 37% (p less than 0.005). A specific zinc effect was observed by a 2-fold increase in tumor weights in repleted rats (p less than 0.05) with marked decreases in tumor necrosis (p less than 0.05) and 29 to 84% increases in tumor zinc concentrations (p less than 0.005). Since there were no decreases in organ weights of zinc-deficient animals and no correlation between final tumor weights and postimplant changes in carcass weights, the results indicate a specific inhibitory effect of zinc deficiency independent of a nonspecific malnutrition.

Anatomic and physiologic age changes in the kidney.

Cross-sectional studies of renal function in man indicate there is a progressive decline with age after the age of 40 years. The blood vessels, glomeruli, tubules and interstitium are all potential sites of primary involvement in the aging process as well as for renal disease. Regardless of the anatomic structure initially affected, most chronic renal conditions evolve with destruction of the entire nephron. Whether the observed decrease in renal function associated with aging is the result of intervening pathologic processes, e.g. ischemia (vascular obliteration) or infection, or is the result of a more insidious involutional process, it has generated much discussion but few answers. The purpose of this report is to review the descriptive studies documenting the changes in renal morphology and physiology with age and to focus on what is known about the mechanisms involved in these losses of renal substances and function.

Longitudinal studies on the rate of decline in renal function with age.

Serial creatinine clearances (5 to 14 studies) were obtained for 446 normal volunteers in the Baltimore Longitudinal Study of Aging followed between 1958 and 1981. When those subjects with possible renal or urinary tract disease and subjects on diuretics and antihypertensives were removed from the study, leaving a group of 254 "normal" subjects, the mean decrease in creatinine clearance was 0.75 ml/min/year. The slopes of the creatinine clearance vs. time fell into a normal (Gaussian) distribution around this mean. One third of all subjects followed had no absolute decrease in renal function (positive slope of creatinine clearance vs. time) and there was a small group of patients who showed a statistically significant increase (P less than 0.05) in creatinine clearance with age.

Alcohol consumption is negatively associated with the prevalence of coronary heart disease in the New Mexico Elder Health Survey.

OBJECTIVE: To compare the prevalence of coronary heart disease (CHD) and the effects of various risk factors, including alcohol consumption, on prevalence rates in a randomly selected sample of older Hispanic and non-Hispanic white (NHW) men and women. DESIGN AND SETTING: A cross-sectional study of equal numbers of Hispanic and NHW men and women, selected randomly from Health Care Financing Authority (Medicare) rolls, recruited for a home interview followed by a 4-hour interview/examination in a senior health clinic. PARTICIPANTS: A total of 883 volunteers, mean age 74.1, years were interviewed/examined. MEASUREMENTS: CHD was identified by interview and electrocardiogram. Risk factors were identified by interview (hypertension, diabetes, medications, smoking, alcohol consumption) and by direct measurements (glucose tolerance, serum lipids, blood pressure, anthropometry). RESULTS: The age-adjusted prevalences of CHD were not significantly different when Hispanic men and women were compared with their NHW counterparts. Age-, ethnicity-, and gender-adjusted relative risk of CHD was inversely associated with alcohol consumption (OR .46; 95% CI, .28-.73; P < .001). Hypertension, diabetes mellitus, and male gender were also significant risk factors; age, anthropometric measurements, smoking, serum lipid concentrations, and level of education were not. HDL cholesterol levels were significantly lower in nondrinkers; other lipid levels were not associated with alcohol consumption. The type of alcoholic beverage was not associated with the prevalence of CHD. CONCLUSIONS: No significant differences in CHD prevalence existed between Hispanic and NHW participants despite a higher prevalence of diabetes and central obesity in Hispanics. Alcohol consumption was strongly negatively associated with the prevalence of CHD identified in this older, biethnic population.

Subclinical hypothyroidism in a biethnic, urban community.

OBJECTIVES: To evaluate the association between hypothyroidism, and the health status of older Hispanic and non-Hispanic white (NHW) men and women. To accomplish this, we determined the prevalences of the treated and untreated conditions and examined the associations between an elevated serum thyroid stimulating hormone (TSH) and cognitive and affective (mood) functions and the prevalences of symptoms and comorbidity, specifically coronary heart disease (CHD), diabetes, hypertension, and hyperlipidemia. DESIGN AND SETTING: A cross-sectional study of equal numbers of Hispanic and NHW men and women selected randomly from the Health Care Financing Administration (Medicare) rolls and recruited for a home interview followed by a 4-hour interview/examination in a senior health clinic. PARTICIPANTS: 883 volunteers, mean age 74.1 years, participated in interviews/examinations MEASUREMENTS: Serum TSH was determined in 825 participants responding to questions about thyroid replacement therapy. Serum free thyroxine (free T4) concentrations were determined in 139 participants with elevated TSH concentrations (>4.6 microU/mL). Symptoms, cognitive tests, a screen for depression, comorbidities (e.g., CHD), and risk factors (e.g., lipid abnormalities, diabetes, and hypertension) were compared in participants with high versus normal TSH values. RESULTS: Subclinical hypothyroidism is more common in women than in men and in non-Hispanic white women compared with Hispanic women. No differences were observed between participants with TSH elevations from 4.7 to 10 microU/mL and those with normal TSH concentrations, and only a few differences were observed in those with TSH concentrations above 10. CONCLUSIONS: Subclinical hypothyroidism is a common condition in community-living older people, especially women. However, it appeared to have no effect on any of the measures of health status utilized until serum TSH concentrations exceeded 10 microU/mL, and even then the effects were rarely significant.

Do elderly persons need to be encouraged to drink more fluids?

BACKGROUND: A recently published and widely quoted modified food guide pyramid encourages persons over the age of 70 years to ingest eight glasses (2 liters) of fluids per day. We challenge the need for this much fluid intake and even question whether it may do more harm than good. METHODS: Equal numbers of Hispanic and non-Hispanic white men and women were selected randomly from the Health Care Financing Administration (Medicare) rolls and recruited for a home interview followed by a 4-hour interview/examination in a senior health clinic. Questionnaires and examinations were used to determine usual daily self-reported intake of fluids, lying and standing blood pressures, history of falls over the past year, and the presence of chronic constipation and chronic fatigue or tiredness. Serum samples were obtained for determination of sodium, urea nitrogen (SUN) and creatinine concentrations, and calculation of SUN/creatinine ratios. RESULTS: Interviews/examinations were conducted on 883 volunteers (mean age of 74.1 years). Most participants (71%) estimated that their usual fluid intake was equal to or exceeded six glasses per day. Evidence of hypernatremia (serum sodium concentration > 146 mEq/l) was not observed in the 227 individuals ingesting less than this. Hyponatremia also was rare in this population. Fluid intake showed no significant associations with lying and standing blood pressures, a history of falling, or the frequency of chronic constipation or fatigue/tiredness. CONCLUSION: Until we have more evidence-based documentation that fluid intake of eight glasses (2 liters) per day improves some aspect of an elderly person's health, encouraging a fluid intake above a level that is comfortable for the individual seems to serve little useful purpose.

Changes in renal function with aging. Implications for treatment.

The most important clinical renal function to monitor with aging is the glomerular filtration rate (creatinine clearance). Most decisions on drug dosage can be based on this information alone as other (tubular) functions of the kidney decrease at rates paralleling the decrease in glomerular filtration rate. As individuals age, mean creatinine clearances fall at a rate approximating 1% per year and there is an increasing variance in creatinine clearances making it increasingly important to adjust drug dosages for changes in renal function. Since muscle mass and urinary creatinine excretions decrease at nearly the same rate, mean serum creatinine concentrations stay nearly constant. One must be aware of this phenomenon when using serum creatinine concentrations alone to determine drug dosages and intervals.

Comparison of energy and nutrient sources of elderly Hispanics and non-Hispanic whites in New Mexico.

OBJECTIVE: Identification and comparison of frequently consumed foods and important food sources of energy, protein, total fat, vitamin A, vitamin C, vitamin E, vitamin B-6, folate, and calcium of elderly Hispanics and non-Hispanic whites. DESIGN: Dietary intake data were collected using a modified Health Habits and History Questionnaire (a food frequency questionnaire) for 735 subjects who participated in the New Mexico Elder Health Survey. SUBJECTS: The sample consisted of 330 Hispanics (176 men and 154 women) and 405 non-Hispanic whites (214 men and 191 women) between the ages of 65 and 96 years. Subjects were those with food frequency data among 883 participants who completed the clinical visit of the New Mexico Elder Health Survey. RESULTS: Results show the top-ranked frequently consumed foods by gender and ethnicity and top-ranked food sources of energy and 8 nutrients. Regional foods were important sources of nutrients in the diets of both Hispanics and non-Hispanic whites, however, more so for the Hispanics. Chile sauces were notable sources of vitamin A, vitamin C, and folate among both groups. Both ethnic groups demonstrated selection of low-fat and skim milk and moderation in consumption of red meat. APPLICATIONS: These data will be useful for designing nutrition education programs, for studying the relationship between diet and disease among elderly Hispanics and non-Hispanic whites, and for designing assessment instruments for the elderly and other ethnic populations.

Assessment of renal function in the old. Special considerations.

The most important clinical renal function to monitor with age is glomerular filtration rate (GFR), as all other changes in renal function tend to parallel changes in GFR. The serum creatinine and creatinine clearance have become the clinical tests most frequently used to measure GFR. The creatinine clearance decreases at a rate approximately 1% per year after age 40 years. Mean serum creatinine values, however, fail to increase with age because creatinine production, which is dependent on muscle mass, falls at nearly the same rate as the renal clearance of creatinine. Serum creatinine concentrations must be interpreted with this in mind when used to determine or modify dosages of drugs cleared totally, for example, the aminoglycoside antibiotics, or partially, for example, digoxin, by the kidney.

Hypokalemia: causes, consequences and correction.

Hypokalemia poses a common diagnostic challenge with many potential etiologies. Multiple factors may contribute to this electrolyte deficiency in any given patient. Gastrointestinal potassium wasting usually is identifiable by an associated increase in fluid losses via biliary tract or bowel. A urinary potassium excretion of 20 mEq or more per day in the presence of a low serum potassium (less than 3.5 mEq/L) suggests inappropriate potassium wasting. Although diuretic therapy (loop diuretics, thiazides) undoubtedly is the most common cause of a potassium deficit, one also must consider abnormalities of the pituitary-adrenal axis, renal disorders including tumors, other drugs, and a variety of less well-defined entities. Potassium deficiency may produce both functional and structural defects in the kidneys, myocardium, skeletal muscle, central nervous system, and gastrointestinal tract. Treatment is aimed at replacing potassium intravenously or orally or preventing further potassium loss (spironolactone, triamterene); when associated with a metabolic alkalosis (chloride deficiency), the replacement should be potassium chloride.

Case report. Severe hyperuricemia, hypokalemic alkalosis and tubulointersitial nephritis.

A patient with severe idiopathic hyperuricemia and hypokalemic alkalosis was followed over a one-year period. A tubulointersitial nephritis consistent with hypokalemic nephropathy was found on biopsy. However, the possibility that the hyperuricemia contributed to the hypokalemia and renal lesion cannot be excluded. Inappropriate urinary loss of potassium could be prevented by administration of spironolactone or triameterene. Six months after initiation of allopurinol therapy with reduction of serum uric acid concentrations to normal concentrations, this potassium wasting was substantially decreased.

Case report: acute pancreatitis following corticosteroid and azathioprine therapy.

Several drugs have been implicated as causes of acute pancreatitis. This report presents four patients, three with lupus nephritis and one with membranous glomerulopathy, who developed acute pancreatitis while being treated with corticosteroids alone or in combination with azathioprine. Two of the reported patients died with a hemorrhagic pancreatitis and one of the patients developed a pancreatic pseudocyst. The pathogenesis of corticosteroid and/or azathioprine-induced pancreatitis is discussed.

Influence of synthetic corticosteroids on plasma zinc and copper levels in humans.

The effects of varying doses of a short-acting (methylprednisolone) and a long-acting (dexamethasone) synthetic glucocorticoid on extent and duration of alterations in plasma zinc and copper concentrations in normal humans are documented. Early after intravenous administration of either steroid, increases in plasma zinc and copper levels were observed. By 12 hours, plasma zinc concentrations had decreased below control levels and the extent and duration of the depression depended on the dosage of the steroid administered. No significant decrease was noted beyond 48 hours. The plasma copper levels did not decrease until after zinc levels began returning toward normal, reaching a peak depression at 48 hours and, at high doses of steroids, persisting until completion of the study at 96 hours. This difference in the time sequence suggests that different mechanism control plasma concentrations of the two metals. The serum zinc levels may depend on ACTH-adrenal interactions, while the slower response of the serum copper levels may depend on changes in the rate of synthesis of the serum copper-binding protein, ceruloplasmin.

Serum concentrations and urinary excretions of zinc in cirrhosis, nephrotic syndrome and renal insufficiency.

Serum zinc conentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy and impaired wound healing) are common in these patients. It remains unresolved whether these low serum zinc concentrations in these disease states are indicative of true symptomatic or asymptomatic zinc deficiency, or merely reflect a decrease in available zinc-binding proteins, as well over 90% of serum zinc is bound to protein in normal subjects. The correlation between serum zinc and albumin concentrations, reportedly the major zinc-binding protein, is unimpressive. Studies of serum and urine binding of added radiozinc65 using Sephadex G-200 gel column chromatography and polyacrylamide gel electrophoresis suggest most of the radiozinc is bound to a protein with a molecular weight near albumin (68,000). Polyacrylamide gel electrophoresis suggests this might be a prealbumin. The low serum zinc concentration in the patient with nephrotic syndrome does not appear to be due to loss of zinc bound to urinary protein.

An etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis); an electron microscopic study.

Renal tissues were studied using electron microscopy (EM) and immunofluorescence microscopy (IFM) from three patients who were found to have chronic interstitial nephritis (pyelonephritis) by light microscopy (LM). By LM, 90% of the glomeruli in two patients and all glomeruli in one patient were normal. By EM, glomerular capillaries in all patients revealed generalized fusion of epithelial foot processes. In two patients, IFM for immunoglobulins, third component of complement and fibrinogen were negative. These two patients received corticosteroids for 6 to 12 weeks. In one, proteinuria markedly decreased (from 17.9 to 1.1 gm) in four weeks and in the other follow-up studies of renal histology revealed normal glomeruli and partial restoration of foot processes by LM and EM respectively. Thus, this study offers evidence for lipoid nephrosis (or minimal lesion disease) as an etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis). The impaired renal function in these patients is attributed to tubulo-interstitial disease rather than glomerular pathology. It remains to be determined whether the two disparate pathological conditions have coexisted or chronic interstitial nephritis had led to the appearance of lipoid nephrosis through an unidentified mechanism.

An electron microscopic technique for the study of elastic tissue in small arteries and arterioles of the kidney.

Elastic tissue content and distribution were studied by electron microscopy of small arteries and arterioles of kidneys obtained from normotensive Wistar and spontaneously hypertensive rats, normal dogs and patients with hypertension and glomerular diseases. Specificity and sensitivity of silver tetraphenyl porphyrin sulfonate stain are discussed. This specific electron microscopy technique should prove useful in analysis of elastic tissue in pathologic states of other organs, especially where elastic tissue normally appears to be sparse or absent.

Rapid development of glomerular crescents in epinephrine-infused dogs.

A serendipitous finding in the kidneys examined by light, electron, and immunofluorescence microscopy (LM, EM, and IFM, respectively) in mongrel dogs infused intravenously with epinephrine (4 microgram per kg per min) alone or in combination with therapeutic agents over a six hour period was proliferating epithelial cells in Bowman's space and adhesion to the Bowman's membrane (crescent). This lesion was observed in 10 of 17 dogs. In five, over 50 percent of the glomeruli were involved. In seven additional dogs infused with epinephrine, renal biopsy studies (LM) at 0, 3 and 6 hr periods revealed crescents only in the six hr specimens. By EM, the crescents were composed of actively proliferating epithelial cells with many large mitochondria containing conspicuous intramitochondrial particles. Fibrin was found within glomerular and peritubular capillaries, within tubules but rarely in the crescent. IFM revealed granular deposits of IgG only in the glomerular basement membrane and mesangium. Other changes included necrosis of the tubules in all dogs receiving epinephrine alone and necrosis of arterioles in some of the dogs studied. Dogs receiving normal saline infusions (control) did not reveal any abnormalities in the kidney. This model should prove useful in determining the morphogenesis of crescent formation and in evaluating the effect of therapeutic agents in the prevention of this lesion.