Leukocyte chemotaxis in diabetic patients and their nondiabetic first-degree relatives.

Leukocyte chemotaxis wasmeasured in 108 subjects: 20 normal controls, 36 insulin-taking diabetics (15 being index patients), and 52 nondiabetic first-degree relatives of index patients. The relatives had a mean chemotactic index (CI) significantly lower than that of the controls (individually, 25 per cent had CIs lower than the lowest of the controls); and the diabetics had a mean CI significantly lower than that of the relatives. The impairment of leukocyte chemotaxis measured in the first-degree relatives of diabetic index patients does not appear to be associated with an increased susceptibility to infection and suggests that the impaired leukotaxis is due to an inherent defect--perhaps genetic--in leukocyte function.

Diabetes mellitus: incidence, prevalence, survivorship, and causes of death in Rochester, Minnesota, 1945-1970.

The incidence and prevalence of diabetes mellitus in residents of Rochester, Minnesota, for 25 years (1945 to 1970) were determined from available medical records. The over-all incidence rate for diabetes is 133 new cases per 100,000 population per year (age-adjusted to 1970 U.S. white population). The rate increased with age for both men and women and was higher among men over 30 years of age. The average annual incidence rates per five-year period for juvenile-onset diabetes mellitus were low and variable and showed little change. Polyuria, polydipsia, glycosuria, lean habitus, loss of weight, and high levels of fasting hyperglycemia at initial diagnosis occurred more frequently in younger than in older patients. The peak incidence in 1960 through 1964 and the decrease in the following five years may be a reflection of the introduction of the AutoAnalyzer method for blood glucose in 1958. The average annual incidence rates for 1955 through 1959 and 1965 through 1969 were essentially the same. The over-all prevalence for diabetes mellitus is 1.6 per cent, with a higher rate among men than among women over 40 years of age; among school children the rate is 0.1 per cent. Survivorship in the diabetic population is lower than that in the general population. The leading cause of death was coronary heart disease, the death rate from it being higher than for the general population.

Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota.

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P less than .01); older age at onset of diabetes (P less than .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

Progression of peripheral occlusive arterial disease in diabetes mellitus. What factors are predictive?

The clinical, biochemical, and vascular laboratory measurements potentially associated with the development and/or progression of peripheral occlusive arterial disease (POAD) were assessed during a 4-year period in 110 normal control subjects, 112 patients with POAD without diabetes mellitus, 240 patients with diabetes mellitus without POAD, and 100 patients with diabetes mellitus and POAD. Age, history of hypertension or coronary heart disease, history of cigarette smoking, presence of POAD, systolic blood pressure, and beta-thromboglobulin level were associated with progression of POAD. A multivariate logistic regression model indicated that the presence of diabetes mellitus or POAD or both at baseline, decreased postexercise ankle-brachial index, increased arm systolic blood pressure, and current smoking were independently associated with progression of POAD. This study suggests that cessation of smoking and control of hypertension are essential treatment modifications to decrease the risk of progression of peripheral vascular disease in diabetic patients.

The contribution of non-insulin-dependent diabetes to lower-extremity amputation in the community.

BACKGROUND: Despite the significant public health burden of lower-extremity amputations in diabetes mellitus, few data are available on the epidemiology of lower-extremity amputations in diabetes mellitus in the community setting. METHODS: A retrospective incidence cohort study based in Rochester, Minn, was conducted. RESULTS: Among the 2015 diabetic individuals free of lower-extremity amputation at the diagnosis of diabetes mellitus, 57 individuals underwent 79 lower-extremity amputations (incidence, 375 per 100,000 person-years; 95% confidence interval, 297 to 467). Among the 1826 patients with non-insulin-dependent diabetes mellitus, 52 underwent 73 lower-extremity amputations, and the subsequent incidence of lower-extremity amputation among these residents was 388 per 100,000 person-years (95% confidence interval, 304 to 487). Of the 137 insulin-dependent diabetic patients, four subsequently underwent five lower-extremity amputations (incidence, 283 per 100,000 person-years; 95% confidence interval, 92 to 659). Twenty-five years after the diagnosis of diabetes mellitus, the cumulative risk of one lower-extremity amputation was 11.2% in insulin-dependent diabetes mellitus and 11.0% in non-insulin-dependent diabetes mellitus. When compared with lower-extremity amputation rates for Rochester residents without diabetes, patients with non-insulin-dependent diabetes mellitus were nearly 400 times more likely to undergo an initial transphalangeal amputation (rate ratio, 378.8) and had almost a 12-fold increased risk of a below-knee amputation (rate ratio, 11.8). In this community, more than 60% of lower-extremity amputations were attributable to non-insulin-dependent diabetes mellitus. CONCLUSIONS: These population-based data document the magnitude of the elevated risk of lower-extremity amputation among diabetic individuals. Efforts should be made to identify more precisely risk factors for amputation in diabetes and to intervene in the processes leading to amputation.

Altering physicians' practice patterns--a nationwide educational experiment: evaluation of the Clinical Education Program of the American Diabetes Association.

A comprehensive evaluation of the Clinical Education Program (CEP) of the American Diabetes Association on type II diabetes was undertaken in a cohort of 5640 primary-care physicians to determine whether practice patterns are affected by such continuing medical education programs. The educational and behavioral objectives were defined and the extent to which these objectives were met was evaluated by use of questionnaires completed by conference attendees both before and after they participated in the program and by in-office interviews 2 mo later with 288 of the primary-care physicians who had attended the conference. Prior to participation, approximately half of the primary-care physicians described diabetes practice patterns consistent with excellent care. The proportion who stated that they intended to improve their practice patterns increased significantly after the conference. Similarly, the majority of these same physicians knew the basic educational objectives before the conference, with a significant increase in the proportion of physicians knowing these objectives after the conference. The office interviews indicated that the changes noted in the proportion of physicians intending to carry out a practice at the end of the conference were sustained or actually increased in this cohort. Exceptions to this trend occurred in the area of use of glucosylated hemoglobin and perhaps in the area of periodic assessment of macrovascular circulation. Two interesting additional findings from the in-office interviews were that physicians prefer the conference format for learning and that distribution of printed material alone is not very effective in influencing knowledge and behavior in primary-care physicians. The CEP met its educational and behavioral objectives.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of diabetes mellitus by clinical type.

The incidence of diabetes mellitus by clinical type was determined for the community of Rochester, Minnesota, 1945-69. Overall adjusted incidence rates per 100,000 person-years were 8.4 for IDDM, 80.1 for obese NIDDM, 45.6 for nonobese NIDDM, and 3.6 for secondary diabetes, using our definitions. Strict use of National Diabetes Data Group criteria would have reduced the apparent incidence of all diabetes by about 20% through the deletion of NIDDM cases. The National Diabetes Data Group classification improved the clinical homogeneity of IDDM patients compared with "juvenile-onset" diabetes but had little effect on NIDDM relative to "maturity-onset" diabetes, since essentially the same patients were included in both groups. Separation of NIDDM into obese and nonobese subcategories accomplished little in the way of defining two more homogeneous subgroups.

A population-based study of diabetes mortality.

In a population-based investigation among the residents of Rochester, Minnesota, the diabetes mortality rate was 8.5 per 100,000 person-years with diabetes as the underlying cause of death, 31.5 per 100,000 person-years with diabetes as an underlying or contributory cause, and 82.7 per 100,000 person-years if all deaths among diabetic individuals were counted. Diabetes was not mentioned on the certificate in 62% of the 428 diabetic deaths during 1965-1974. When the clinical characteristics of the subgroup of mortality cases in 1969 were compared with those of the prevalence cases on 1 January 1970, it was found that mortality cases tended to be older, were more often on insulin therapy, and were more likely to have macro- and microvascular complications. Because mortality data are sometimes used to infer trends and characteristics for the diabetic population at large, it is important to recognize these biases.

Insulin therapy for diabetic ketoacidosis. Bolus insulin injection versus continuous insulin infusion.

OBJECTIVE: Despite widespread acceptance of continuous insulin infusion (CII) over bolus insulin injection (BII) for treatment of diabetic ketoacidosis (DKA), there are no population-based studies demonstrating whether CII has resulted in lower morbidity and mortality. RESEARCH DESIGN AND METHODS: We addressed this issue using a provider-linked database and retrospectively reviewing the complete medical records of all incidence cases of diabetes among Rochester, Minnesota, residents from 1950 to 1989 with a discharge diagnosis of DKA. This population-based study describes the consequences of the widespread change in treatment modality outside the confines of a controlled clinical trial. RESULTS: Among the diabetes incident cohort, there were 59 subjects with confirmed first episodes of DKA during 1950-1992; 29 of 30 subjects treated with BII occurred before 1970. All 29 CII cases occurred between 1976 and 1992. Sex, etiology, diabetes duration, and age at DKA were similar for the two groups. The proportion of obese individuals (BII = 2/28, CII = 8/21; P = 0.01) differed between groups. The CII group exhibited higher glucose values (BII = 24.9 +/- 8.5 mmol/l, CII = 37.1 +/- 15.1 mmol/l; P = 0.002) and lower bicarbonate values (BII = 7.7 +/- 3.0 nmol/l, CII = 6.2 +/- 2.9 nmol/l; P = 0.04) upon admission. The mean quantity of insulin administered was higher in the BII group than in the CII group (179 +/- 140 and 99 +/- 70 U, P < 0.006). The outcome of hypoglycemia occurred more frequently in the BII group than in the CII group (BII = 8/30, CII = 1/29; P = 0.03). The proportion with hypokalemia, neurological deficit, myocardial arrhythmia, or mortality did not differ significantly between groups. CONCLUSIONS: Our findings suggest the introduction of CII was accompanied by a decreased incidence of hypoglycemia.

Referral bias in diabetes research.

Of all the known diabetic individuals residing in the community of Rochester, Minnesota, only about one-half would have been recognized through a review of the medical records of 1 yr. Only one-fifth of the diabetic residents were hospitalized during the index year and a similarly small proportion were attended in a diabetes clinic. This selective process produced distortion in the apparent clinical spectrum of diabetes observed at different levels in the medical care system. Notable was overestimation of the relative importance of insulin-dependent diabetes and of the vascular complications of diabetes among hospital and diabetes clinic patients. Referral bias should be taken into account when differences are noted in the epidemiologic features of diabetes as reported from different types of medical care settings.

Sources of disparity in the spectrum of diabetes mellitus at incidence and prevalence.

In a population-based study in Rochester, Minnesota, the clinical characteristics of 1135 patients newly diagnosed with diabetes (1945-69) were compared with those of 810 residents with diabetes mellitus on prevalence day (1 January 1970). The prevalence patients were older and the male: female ratio was reduced from that seen among incidence cases. The prevalence patients were more likely to be on oral agents, had lower fasting blood glucose levels, were less likely to be symptomatic, but were more likely to have macrovascular and microvascular complications. These differences seemed to come about as a result of variation in survival rates among patients with specific characteristics, differential migration of certain groups of patients, and changes in the status of individuals.

Incidence and prevalence of clinical peripheral vascular disease in a population-based cohort of diabetic patients.

Clinical peripheral vascular disease (PVD) was studied in an incidence cohort of 1073 residents of Rochester, Minnesota, who were found to have diabetes mellitus in the period 1945-69. About 8% of patients already had clinical evidence of PVD at the time of diagnosis of diabetes. The proportion increased with the age at which diabetes was discovered. Among those unaffected initially, the incidence of subsequent PVD was slightly greater for men, 21.3 per 1000 person-years, than for women, 17.6 per 1000, and it increased both with age and duration of diabetes. The cumulative incidence of subsequent PVD was estimated to be 15% at 10 yr and 45% at 20 yr after the diagnosis of diabetes. The age-adjusted prevalence of residents with diabetes and a history of PVD was 3.3 per 1000 population 30 yr of age or over on 1 January 1970.

Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota.

Among the 1135 Rochester residents discovered to have diabetes in the period 1945-69, the prevalence of retinopathy was 2.6% at the time of initial diagnosis. Among those free of retinopathy at diagnosis of diabetes, the subsequent incidence of any retinopathy was 17.4 per 1000 person-years and for proliferative retinopathy alone was 1.6 per 1000 person-years, based on 12,000 person-years of follow-up. The incidence rate of retinopathy was almost three times greater among residents with insulin-dependent (IDDM) than with non-insulin-dependent diabetes (NIDDM); however, the actual number of retinopathy cases was over four times greater among the more numerous residents with NIDDM. By 20 yr after diagnosis of diabetes, the cumulative incidence of retinopathy approached 70% among IDDM subjects and was 30% and 36%, respectively, among the obese and nonobese NIDDM residents. The epidemiologic patterns for proliferative retinopathy were qualitatively similar to those for nonproliferative retinopathy. The risk of blindness was greater among those with proliferative than with nonproliferative retinopathy but was substantial even for those without retinopathy. Most blindness was caused by factors other than isolated diabetic retinopathy.

Course of peripheral occlusive arterial disease in diabetes. Vascular laboratory assessment.

To determine comparative rates of development and progression of peripheral occlusive arterial disease, 110 healthy nondiabetic control subjects, 112 patients with peripheral occlusive arterial disease (POAD), 240 patients with diabetes mellitus (DM), and 100 patients with diabetes mellitus and peripheral occlusive arterial disease (DM + POAD) were studied over 4 yr with noninvasive techniques. The presence of peripheral occlusive arterial disease was determined by postexercise ankle-brachial index (ABI) values; progression of peripheral occlusive arterial disease was determined by the rate of change in postexercise ABI. Patients who underwent peripheral arterial reconstructive surgery or amputation were also classified as having progression of their peripheral occlusive arterial disease. On this basis, follow-up revealed that peripheral occlusive arterial disease developed and therefore progressed in 1 (1%) of the control group and 22 (9%) of the DM. Peripheral occlusive arterial disease progressed in 31 (28%) of the POAD and 26 (26%) of the DM + POAD. The presence of peripheral occlusive arterial disease predisposes to progression of disease, and peripheral occlusive arterial disease is more likely to develop in diabetic patients who do not have peripheral occlusive arterial disease than in nondiabetic control subjects. However, the presence of diabetes mellitus in patients with peripheral occlusive arterial disease does not seem to increase the risk of progression.

Temporal trends in BMI among adults with diabetes.

OBJECTIVE: Increasing obesity within the general population has been accompanied by rising rates of diabetes. The extent to which obesity has increased among people with diabetes is unknown, as are the potential consequences for diabetes outcomes. RESEARCH DESIGN AND METHODS: Community medical records (hospital and ambulatory) of all Rochester, Minnesota, residents aged > or =30 years who first met standardized research criteria for diabetes from 1970 to 1989 (n = 1,306) were reviewed to obtain data on BMI and related characteristics as of the diabetes identification date (+/-3 months). Vital status as of 31 December 1999 and date of death for those who died were obtained from medical records, State of Minnesota death tapes, and active follow-up. RESULTS: As of the identification date, data on BMI were available for 1,290 cases. Of the 272 who first met diabetes criteria in 1970-1974, 33% were obese (BMI > or =30), including 5% who were extremely obese (BMI > or =40). These proportions increased to 49% (P < 0.001) and 9% (P = 0.012), respectively, for the 426 residents who first met diabetes criteria in 1985-1989. BMI increased significantly with increasing calendar year of diabetes identification in multivariable regression analysis. Analysis of survival revealed an increased hazard of mortality for BMI > or =41, relative to BMI of 23-25 (hazard ratio 1.60, 95% CI 1.09-2.34, P = 0.016). CONCLUSIONS: The prevalence of obesity and extreme obesity among individuals at the time they first met criteria for diabetes has increased over time. This is disturbing in light of the finding that diabetic individuals who are extremely obese are at increased risk of mortality compared with their nonobese diabetic counterparts.

Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota.

Retinopathy is an important sequela of diabetes mellitus, but clinical risk factors for this condition have rarely been assessed in a geographically defined population. In this population-based study, the 1135 Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort) were followed through their complete medical records in the community to January 1, 1982. Because most of the cases of diabetic retinopathy in Rochester residents developed in patients with non-insulin-dependent diabetes mellitus (NIDDM), risk factors for diabetic retinopathy were examined in this group (N = 1031). A proportional hazards model identified the following risk factors for diabetic retinopathy in NIDDM: elevated initial fasting blood glucose level, marked obesity, and earlier age at onset of diabetes. Stratified analyses indicated that duration of diabetes was also significantly associated with an increased risk of retinopathy. Two secular trends, increasing detection of "mild" NIDDM and decreasing risk of diabetic retinopathy, had a major effect on retinopathy risk assessment. These data also suggest that insulin therapy is not an independent risk factor for diabetic retinopathy.

Trends in persistent proteinuria in adult-onset diabetes: a population-based study.

OBJECTIVE: This study investigates temporal trends in the prevalence and incidence of persistent proteinuria among people with adult-onset diabetes (age > or =40 years). RESEARCH DESIGN AND METHODS: The complete community-based medical records of all Rochester, Minnesota, residents with a diagnosis of diabetes or diabetes-like condition from 1945 through 1989 were reviewed to determine whether they met National Diabetes Data Group (NDDG) criteria. All confirmed diabetes cases residing in Rochester on 1 January 1970 (n = 446), 1980 (n = 647), and/or 1990 (n = 940) were identified. The medical records of these prevalence cases were reviewed from the time of the first laboratory urinalysis value to the last visit, death, or 1 April 1992 (whichever came first) for evidence of persistent proteinuria (two consecutive urinalyses positive for protein, with no subsequent negative values). Similarly, the medical records of all 1970-1989 diabetes incidence cases (n = 1,252) were reviewed to investigate temporal changes in 1) the likelihood of having persistent proteinuria before the date NDDG criteria was met, i.e., baseline; 2) the risk of persistent proteinuria after baseline; and 3) the relative risk of mortality associated with persistent proteinuria. RESULTS: The proportion of diabetes prevalence cases with persistent proteinuria on or before the prevalence date declined from 20% in 1970 to 11% in 1980 and 8% in 1990. Among the 1970-1989 diabetes incidence cases, 77 (6%) had persistent proteinuria on or before baseline; the adjusted odds declined by 50% with each 10-year increase in baseline calendar year (P<0.001). Among individuals free of persistent proteinuria at baseline, 136 subsequently developed persistent proteinuria; the estimated 20-year cumulative incidence was 41% (95% CI 31-59); the adjusted risk did not differ as a function of baseline calendar year. Survival of individuals with persistent proteinuria relative to those without was reduced but did not differ by baseline calendar year. CONCLUSIONS: The prevalence of persistent proteinuria among people with adult-onset diabetes in Rochester, Minnesota, declined 60% between 1970 and 1990. The decline appears because of a decrease in the proportion of diabetes incidence cases with persistent proteinuria before baseline rather than secular declines in the risk of persistent proteinuria after baseline or secular increases in the risk of mortality associated with persistent proteinuria. Similarity over time in age and fasting glucose at baseline, and at prevalence dates, is evidence that earlier detection of diabetes is not the sole explanation for the decline.

Glucagon-sensitive adenylate cyclase in human renal medulla.

In cell-free preparations (washed 600 x g pellets) of human renal medulla, glucagon produced a dose-dependent stimulation of adenylate cyclase. The stimulation of renal medullary adenylate cyclase by saturating concentrations of glucagon was additive to the saturating doses of vasopressin. Furthermore, L-isoproterenol stimulated renal medullary adenylate cyclase in a dose-dependent manner, and this stimulation was blocked by DL-propranolol. Stimulation of the renal medullary adenylate cyclase by maximal doses of glucagon and L-isoproterenol was additive. DL-Propranolol did not inhibit stimulation of glucagon. Thus, the results indicate the existence of a specific adenylate cyclase that is responsive to glucagon--distinct from the isoproterenol-sensitive adenylate cyclase and the previously described vasopressin-sensitive adenylate cyclase in human renal medulla. We suggest that the renal tubular effect of glucagon may be mediated by glucagon-dependent cyclic-AMP production in renal tissue.

Sucrose sensitivity of patients with coronary artery disease.

Various loads of simple carbohydrates were fed to 148 patients with known coronary-artery disease (CAD) for 4 days in the Clinical Research Center. The 148 patients were grouped according to the diet regimen tested-sucrose (low and high), glucose, and fructose. A high-sucrose diet was fed to 29 control subjects. Diets containing 2 g of simple carbohydrate (predominantly either sucrose or glucose) per kilogram of body weight per day had no significant effect on fasting plasma glucose, serum triglycerides, or serum free fatty acids. However, diets containing 4 g of simple carbohydrate (predominantly sucrose) or 2 g fructose per kilogram of body weight per day produced a significant rise in serum triglycerides with decreases in fasting plasma glucose and free fatty acids. Serum cholesterol diminished in all the diet groups, probably because of the decrease fat and cholesterol intakes. The increase of serum triglycerides in CAD patients receiving simple carbohydrate at the 4-g/kg rate was significantly greater than in the normal control subjects fed the same diet, suggesting a sensitivity of CAD patients to this stimulus. No significant correlation could be demonstrated between changes in serum triglycerides and the extent of CAD (one, two, or three vessels) as determined from coronary angiograms.

Sterol excretion and cholesterol absorption in diabetics and nondiabetics with and without hyperlipidemia.

Fecal neutral and acidic sterols and cholesterol absorption were measured in 12 normal control subjects, 40 diabetic subjects with and without hyperlipidemia, and 27 subjects with hyperlipidemia but without diabetes mellitus. All subjects were on a low-cholesterol diet (less than 300 mg cholesterol/day). Fecal excretion of neutral and acidic sterols was increased in patients with hypertriglyceridemia and was more marked in diabetic patients with hypertriglyceridemia. Cholesterol absorption was decreased in diabetic patients with hypertriglyceridemia. Otherwise, there were no significant differences in sterol excretion or cholesterol absorption in diabetic and nondiabetic subjects compared with control groups with similar lipid levels. The best predictors of fecal neutral- and acidic-sterol excretion and of estimated cholesterol synthesis were very low [corrected]-density lipoprotein triglycerides and high-density lipoprotein cholesterol. Correction of hyperlipidemia may be beneficial in decreasing cholesterol synthesis and, thereby, in decreasing the risk of atherogenesis.