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Biomedical subjects

M L Sievers

Publications and source records attributed to M L Sievers.

At least 19 recordsLinked to original sources
PubMed1996

HLA*A2 confers mortality risk for cardiovascular disease in Pimans.

A sample of 1465 full heritage Piman Indians from Arizona were typed for the serological antigens of the HLA class I loci and then incorporated into a survival study that ended December 31, 1991. The total follow-up time was 11,749 person-years with an average of 8.0 years per person. During the study 298 persons died, 54 from cardiovascular disease (CVD). Allele HLA*A2 conferred a 4.94 fold rate for death from CVD (95% C.I. 1.91-12.77). When controlled for the potential confounding variables, cholesterol, mean blood pressure, smoking, body mass index, rheumatoid factor titer, and nephropathy, the mortality rate ratio (MRR) was 5.42 (95% C.I. 1.98-14.82). There was no statistically significant association of mortality with other HLA-A or HLA-B alleles, or for causes of death not related to cardiovascular disease.

Adult↗
PubMed1996

Sequential trends in overall and cause-specific mortality in diabetic and nondiabetic Pima Indians.

OBJECTIVE: To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: Underlying causes of death in Pimas aged > or = 15 years old were determined for the years 1975-1989 from review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals. RESULTS: The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70-1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74-1.1). Among diabetic Pimas, however, the death rate for diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33-0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91-2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents. CONCLUSIONS: The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend.

Adolescent↗
PubMed1993

Determinants of end-stage renal disease in Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus and proteinuria.

To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio > or = 0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61% 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61%) than in Caucasians from Rochester, Minnesota (17%) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease.

Adult↗
PubMed1992

Impact of NIDDM on mortality and causes of death in Pima Indians.

OBJECTIVE: To compare overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: This community-based study determined overall and cause-specific death rates in persons with and without NIDDM in the Pima population. Underlying causes of death for the 10-yr period from 1975 to 1984 were derived from review of death certificates and medical records. Diabetes diagnoses were based on an ongoing diabetes study initiated by the National Institutes of Health in 1965. RESULTS: Of the 512 deaths, 241 were in Pima Indians with NIDDM; 203 (84%) of the deaths in diabetic subjects were attributed to natural causes (46 diabetic nephropathy, 35 IHD, 29 infections, 20 malignant neoplasms, 20 alcoholic liver disease, 18 stroke, 35 other causes). For natural causes, the overall age-sex-adjusted death rate in diabetic subjects was 1.7 times (95% CI 1.4-2.2) that in nondiabetic subjects. Longer duration of diabetes was significantly related to mortality, an association that was stronger in women than in men. Rates of death from diabetic nephropathy, IHD, and infections (but not stroke) were each significantly related to longer diabetes duration. Together, diabetic nephropathy and IHD accounted for 90% of the excess death rate among diabetic, compared with nondiabetic, Pimas. CONCLUSIONS: In Pima Indians, NIDDM has a significant adverse effect on death rates that is directly related to diabetes duration, especially for deaths from diabetic nephropathy, IHD, or infections. Among the Pima, diabetic nephropathy is the leading cause of death, and IHD ranks second--a variation from other populations (in which IHD ranks first), probably partly attributable to a much younger age of onset of diabetes among the Pima than in the U.S. white population.

Adolescent↗
PubMed1990

Adverse mortality experience of a southwestern American Indian community: overall death rates and underlying causes of death in Pima Indians.

As part of an ongoing epidemiologic study, the death rate and causes of death during 1975 through 1984 were determined in Pima Indians who resided in the Gila River Indian Community (GRIC) in 1965 and later. Death certificates were available for 677 of the 681 deaths. In 78% of the deaths, the underlying cause recorded on the death certificate agreed with the cause determined after review of all available relevant records. The age- and sex-adjusted average annual death rate for the GRIC population (1639/100,000) was 1.9 times (95% CI 1.7-2.0) the 1980 rate for the U.S. all races (878/100,000). In Pima males, whose death rate was substantially higher than that of Pima females, the age-adjusted death rate was 2.3 times that in U.S. males, all races. Moreover among males 25-34 years of age, the Pima death rate was 6.6 times that for the U.S. all races. Diseases of the heart and malignant neoplasms caused 59% of U.S. deaths in 1980, but only 19% of GRIC deaths. By contrast, the age- and sex-adjusted mortality rate in the GRIC Pima was 5.9 times the rate of the U.S. all races for accidents, 6.5 times for cirrhosis, 7.4 times for homicide, 4.3 times for suicide, and 11.9 times for diabetes. Tuberculosis and coccidioidomycosis were important causes of death in the Pima, for whom infectious diseases was the tenth leading cause of death. The findings indicate that programs to improve the adverse mortality experience of the GRIC population should emphasize factors related to fatal accidents, alcoholic cirrhosis, homicide, suicide, diabetes mellitus, and infectious diseases. Young Pimas, especially the males, should be the primary focus of such preventive efforts. These findings and recommendations probably apply to many Native American populations.

Accidents↗
PubMed1990

Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes.

The incidence of fatal coronary heart disease (CHD) was determined in a population of Pima Indians from the Gila River Indian Community in Arizona. Between 1975 and 1984, 394 deaths occurred among 4,828 subjects aged 5 years or older, and 199 of these occurred in the 1,093 persons with non-insulin-dependent diabetes. Only 28 deaths were attributed to CHD; all occurred among the 689 diabetic persons 45 years of age or older. No CHD deaths occurred among the 419 nondiabetic subjects 45 years of age or older. The rate of fatal CHD among the diabetic subjects was higher in men than in women and increased with advancing age and duration of diabetes. A higher incidence of fatal CHD was associated with proteinuria, renal insufficiency, medial arterial calcification, diabetic retinopathy, insulin therapy, and an abnormal electrocardiogram. In Pima Indians aged 50-79 years, the incidence of fatal CHD was less than half that found in the Framingham population after controlling for age, sex, and diabetes (incidence rate ratio, 0.4; 95% confidence interval, 0.2-0.7). Factors protecting Pima Indians from fatal CHD may include racial heritage, low serum concentrations of total and low density lipoprotein cholesterol, and rarity of heavy smoking. Among the diabetic subjects, mortality from diabetic renal disease, which shows many of the same risk factors, may selectively compete and remove those at risk for fatal CHD. This would not, however, explain the lack of fatal CHD among the nondiabetic subjects. Fatal CHD shares many of the risk factors associated with the specific microvascular complications of diabetes, and diabetes and its associated attributes are the major predictors of fatal CHD in this population.

Aged↗
PubMed1988

Incidence of end-stage renal disease in type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians.

The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p less than 0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0-5 years to 40.8 cases/1000 person-years at greater than or equal to 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared.

Age Factors↗
PubMed1984

Low acid output in Pima Indians. A possible cause for the rarity of duodenal ulcer in this population.

Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indians and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the Caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of acaloric liquid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and a slow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased prevalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.

Achlorhydria↗
PubMed1984

Gastric function and obesity: gastric emptying, gastric acid secretion, and plasma pepsinogen.

Because rapid gastric emptying and a shortened satiety period might contribute to development of obesity, this study compared gastric emptying of acaloric liquid, gastric acid production, and plasma levels of gastrin and pepsinogen I (PG I) and II (PG II) among obese and nonobese Pima Indians. Rates of fractional gastric emptying and of gastric acid secretion were similar in the two groups, basally and after an acaloric liquid meal. Basal and postprandial plasma gastrin levels did not differ significantly in obese and nonobese Pimas , but peak betazole-stimulated gastric acid output was greater in the obese group, except when normalized by body weight. The plasma PG I and PG II concentrations and PG I/PG II ratio did not differ significantly between the two groups, but the PG I/PG II ratio had a positive correlation with peak acid output. No correlation was found between fractional gastric emptying rate and degree of obesity. We conclude that an increased gastric emptying rate for liquid does not contribute to the pathogenesis of obesity in Pima Indians.

Adolescent↗
PubMed1983

Inhibitory effect of intragastric glucose on gastric acid secretion and gastric emptying of liquids in man. Role of endogenous somatostatin, gastrin, and insulin.

Intragastric glucose inhibits gastric acid secretion and gastric emptying in man. To determine if these effects are mediated by somatostatin--a known inhibitor of gastric acid production, gastrin secretion, and gastric motility--the plasma somatostatin-like immunoreactivity (SLI) levels were determined in healthy human subjects after an intragastric load of 30% glucose solution. These findings were compared with results after an instillation of distilled water. Following the glucose load, the intragastric acid concentration, the acid output, and the fractional gastric emptying rate declined significantly (P less than 0.01) before either the plasma glucose or plasma insulin levels had increased. Neither the gastrin nor SLI plasma concentrations changed after the water or glucose load. These findings suggest that the suppression of gastric acid secretion and inhibition of the rate of gastric emptying that occur with intragastric glucose are mediated by factors other than changes in the peripheral circulating levels of SLI, gastrin, insulin, or glucose.

Adult↗
PubMed1983

Hyperinsulinemia in obesity: lack of relation to gastric emptying of glucose solution or to plasma somatostatin levels.

To investigate some factors that may be related to the hyperinsulinemia of obesity, we measured fractional gastric emptying rates and changes of circulating levels of glucose, insulin, and somatostatin-like immunoreactivity (SLI) following the intragastric instillation of glucose in age-matched obese and nonobese Pima Indians with normal glucose tolerance. Results for the nonobese Pimas were also compared with findings for age- and weight-matched Caucasians with normal glucose tolerance. The levels of fasting plasma insulin and the integrated insulin response to glucose were significantly greater (P less than 0.01) in obese than in nonobese Pimas. Mean rates of fractional gastric emptying, both in the basal state and after the glucose load, were similar for the three groups. The fractional gastric emptying rates after a glucose load were strongly correlated with the integrated responses of both plasma glucose and insulin in the nonobese Caucasians (r = 0.88, 0.90; P less than 0.01) but not in either Pima group. There were no significant differences in peripheral plasma SLI for any of the three groups, either in the basal state or after the glucose load. These findings suggest that the hyperinsulinemia of established obesity is not mediated by alterations in the gastric emptying rate of liquids or by peripheral plasma SLI concentrations. They do not, however, exclude defects in gastric emptying of solid foods. Nor do they exclude the possibility that gastric or D-cell abnormalities exist during the period of fat accumulation but recede after obesity is established.

Adult↗
PubMed1983

Hypergastrinemia in obese noninsulin-dependent diabetes: a possible reflection of high prevalence of vagal dysfunction.

To elucidate the relation of noninsulin-dependent (type II) diabetes mellitus to plasma levels of gastrin, pepsinogen I, and pepsinogen II, gastric acid secretion, and gastric emptying, we studied diabetic and nondiabetic obese Pima Indian subjects. Fasting and postprandial plasma gastrin concentrations were significantly higher (P less than 0.02) in diabetic than in nondiabetic subjects, but gastric acid outputs basally, after an acaloric liquid meal, and in response to betazole were similar in the two groups. Plasma pepsinogen I and pepsinogen II levels were also similar in both groups. A significant negative relation (r = -0.84; P less than 0.01) was found between basal gastrin levels and gastric acid production in nondiabetic Indians, but not in diabetic Pimas. The fractional gastric emptying rate of an acaloric liquid meal was significantly decreased in diabetic Pimas (P less than 0.01); and at least one test showing abnormal vagal function, as estimated by the Valsalva maneuver, heart rate changes between deep expiration and inspiration, and postural hypotension, was found in every diabetic subject. These findings suggest that hypergastrinemia in type II diabetes is not related to hypochlorhydria, but, instead, results from autonomic dysfunction with slow gastric emptying.

Adult↗
PubMed1982

Decreasing incidence of disseminated coccidioidomycosis among Piman and San Carlos Apache Indians. A probable environmental basis.

Among Piman and San Carlos Apache Indians, the rates of disseminated disease and death from coccidioidomycosis have declined 67 percent (p less than 0.001) and 71 percent (p less than 0.01), respectively, between the first and second half of a 22-year observation period (1959-1980), despite a lack of significant change in the rate of primary infection (as determined by the coccidioidin skin test) between the two 11-year periods. The two tribal groups studied comprised 76 percent of the Indian population in the endemic area. More than 90 percent of Pimans and San Carlos Apaches have full Indian heritage, and almost all of them have been lifelong inhabitants of the endemic region. There is no evidence that genetic factors are responsible for the Indians' decrease in mortality and mortality from disseminated coccidioidomycosis. Improvements in housing and working conditions appear to have lessened the exposure to dust laden with C immitis, decreased the size of infecting inoculum, and, thereby, contributed to a decline in disseminated coccidiodomycosis among these native Americans, who have often been considered to have increased susceptibility to this fungal infection. Thus, the outcome of coccidioidal infection in American Indians seems to be largely determined by environmental influences. The possibility of decreasing disseminated disease rates by reducing the inhalation of arthroconidia also has important implications for other ethnic groups.

Adolescent↗