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Biomedical subjects

William H Herman

Publications and source records attributed to William H Herman.

At least 19 recordsLinked to original sources
PubMed2006

Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.

BACKGROUND: The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known. METHODS: We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter (10.0 mmol per liter), for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin, insulin sensitivity, and beta-cell function. RESULTS: Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide (P<0.001 for all comparisons). CONCLUSIONS: The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00279045 [ClinicalTrials.gov].).

Cardiovascular Diseases↗
PubMed2006

The influence of maternal weight and glucose tolerance on infant birthweight in Latino mother-infant pairs.

OBJECTIVES: We assessed the influence of maternal anthropometric and metabolic variables, including glucose tolerance, on infant birthweight. METHODS: In our prospective, population-based cohort study of 1041 Latino mother-infant pairs, we used standardized interviews, anthropometry, metabolic assays, and medical record reviews. We assessed relationships among maternal sociodemographic, prenatal care, anthropometric, and metabolic characteristics and birthweight with analysis of variance and bivariate and multivariate linear regression analyses. RESULTS: Forty-two percent of women in this study entered pregnancy overweight or obese; at least 36% exceeded weight-gain recommendations. Twenty-seven percent of the women had at least some degree of glucose abnormality, including 6.8% who had gestational diabetes. Maternal multiparity, height, weight, weight gain, and 1-hour screening glucose levels were significant independent predictors of infant birthweight after adjustment for gestational age. CONCLUSION: Studies of birthweight should account for maternal glucose level. Given the increased risk of adverse maternal and infant outcomes associated with excessive maternal weight, weight gain, and glucose intolerance, and the high prevalence of these conditions and type 2 diabetes among Latinas, public health professionals have unique opportunities for prevention through prenatal and postpartum interventions.

Adult↗
PubMed2006

Missed opportunities for type 2 diabetes mellitus screening among women with a history of gestational diabetes mellitus.

OBJECTIVES: We sought to determine rates and factors associated with screening for type 2 diabetes mellitus (DM) in women with a history of gestational diabetes mellitus. METHODS: We retrospectively studied women with diagnosed gestational diabetes mellitus who delivered at a university-affiliated hospital (n=570). Data sources included medical and administrative record review. Main outcome measures were the frequency of any type of glucose testing at least 6 weeks after delivery and the frequency of recommended glucose testing. We assessed demographic data, past medical history, and prenatal and postpartum care characteristics. RESULTS: Rates of glucose testing after delivery were low. Any type of glucose testing was performed at least once after 38% of deliveries, and recommended glucose testing was performed at least once after 23% of deliveries. Among women with at least 1 visit to the health care system after delivery (n=447), 42% received any type of glucose test at least once, and 35% received a recommended glucose test at least once. Factors associated with testing were being married, having a visit with an endocrinologist after delivery, and having more visits after delivery. CONCLUSIONS: These findings suggest that most women with gestational diabetes mellitus are not screened for type 2 DM after delivery. Opportunities for DM prevention and early treatment are being missed.

Adult↗
PubMed2006

A discrete-state discrete-time model using indirect observation.

This research was motivated by a desire to model the progression of a chronic disease through various disease stages when data are not available to directly estimate all the transition parameters in the model. This is a common occurrence when time and expense make it unfeasible to follow a single cohort to estimate all the transition parameters. One difficulty of developing a model of chronic disease progression from such data is that the available studies often do not include the transitions of interest. For example, in our model of diabetic nephropathy, many clinical studies did not differentiate between patients without nephropathy and those who had microalbuminuria (a pre-clinical stage of nephropathy). Another difficulty was a lack of data to directly estimate parameters of interest. We consider models which can accommodate such difficulties. In this paper we consider the problem of estimating parameters of a discrete-time Markov process when longitudinal data describing the entire process are not available. First, we present a likelihood approach to estimate parameters of a discrete-time Markov model. Next, we use simulation to investigate the finite-sample behaviour of our approach. Finally, we present two examples: a model of diabetic nephropathy and a model of cardiovascular disease in diabetes.

Albuminuria↗
PubMed2006

The association between clinical care strategies and the attenuation of racial/ethnic disparities in diabetes care: the Translating Research Into Action for Diabetes (TRIAD) Study.

OBJECTIVE: We sought to determine whether greater implementation of clinical care strategies in managed care is associated with attenuation of known racial/ethnic disparities in diabetes care. RESEARCH DESIGN AND METHODS: Using cross-sectional data, we examined the quality of diabetes care as measured by frequencies of process delivery as well as medication management of intermediate outcomes, for 7426 black, Latinos, Asian/Pacific Islanders, and white participants enrolled in 10 managed care plans within 63 provider groups. We stratified models by intensity of 3 clinical care strategies at the provider group level: physician reminders, physician feedback, or use of a diabetes registry. RESULTS: Exposure to clinical care strategy implementation at the provider group level varied by race and ethnicity, with <10% of black participants enrolled in provider groups in the highest-intensity quintile for physician feedback and <10% of both black and Asian/Pacific Islander participants enrolled in groups in the highest-intensity quintile for diabetes registry use. Although disparities in care were confirmed, particularly for black relative to white subjects, we did not find a consistent pattern of disparity attenuation with increasing implementation intensity for either processes of care or medication management of intermediate outcomes. CONCLUSIONS: For the most part, high-intensity implementation of a diabetes registry, physician feedback, or physician reminders, 3 clinical care strategies similar to those used in many health care settings, are not associated with attenuation of known disparities of diabetes care in managed care.

Cross-Sectional Studies↗
PubMed2006

Lifestyle intervention to prevent diabetes: intensive and cost effective.

PURPOSE OF REVIEW: Type 2 diabetes is a major cause of morbidity and mortality, and despite treatment advances appears to be increasing in incidence. Since individuals at risk for the disease are usually identifiable in the prediabetic phase of impaired glucose tolerance, early intervention might prevent diabetes and hence its complications from developing. Obesity and sedentary living are powerful determinants of diabetes, and thus lifestyle change is a logical approach to prevention of this disease. Recent clinical trials have now tested the effectiveness of this intervention and form the basis for this review. RECENT FINDINGS: Three clinical trials have demonstrated that, compared with usual care, lifestyle intervention significantly reduced progression rates to diabetes in prediabetic individuals. Each trial incorporated individualization and repeated long-term contacts with facilitators, in which dietary and physical activity goal setting and behavior modification were central themes. Progression to diabetes was reduced in the Da Qing study by approximately 40%, in the Finnish Diabetes Prevention Study by 58% and in the Diabetes Prevention Program by 58%. The Diabetes Prevention Program included a cost-benefit unit that estimated the per capita costs of the lifestyle intervention to exceed that of the usual care group by Dollars 3540, which translated to a cost of Dollars 15,700 per case of diabetes prevented. Lifetime cost-utility analysis demonstrated an overall cost of Dollars 1100 per quality-adjusted life year. SUMMARY: These findings make the case for translation of research findings to healthcare systems. Although there is more to be learned about effective strategies in clinical practice, it seems clear that the intervention needs to incorporate individualization and long-term interaction with trained facilitators.

Adult↗
PubMed2006

Cost-utility analysis in a UK setting of self-monitoring of blood glucose in patients with type 2 diabetes.

BACKGROUND: Self-monitoring of blood glucose (SMBG) in type 2 diabetes patients has been shown in meta-analyses of randomized trials to improve HbA(1c) by approximately 0.4% when compared to no SMBG. However, the cost of testing supplies is high, improvements in health utility due to improved glycaemic control may be possible and cost-effectiveness has not been evaluated. METHODS: A peer-reviewed validated model projected improvements in lifetime quality-adjusted life years (QALYs), long-term costs and cost-effectiveness of SMBG versus no SMBG. Markov/Monte Carlo modelling simulated the progression of complications (cardiovascular, neuropathy, renal and eye disease). Transition probabilities and HbA(1c)-dependent adjustments came from the United Kingdom Prospective Diabetes Study (UKPDS) and other major studies. Effects of SMBG on HbA(1c) came from clinical studies, meta-analyses and population studies, but can only be considered 'moderate' levels of evidence. Costs of complications were retrieved from published sources. Direct costs of diabetes complications and SMBG were projected over patient lifetimes from a UK National Health Service perspective. Outcomes were discounted at 3.5% annually. Extensive sensitivity analyses were performed. RESULTS: Depending on the type of diabetes treatment (diet and exercise/oral medications/insulin), improvements in glycaemic control with SMBG improved discounted QALYs anywhere from 0.165 to 0.255 years, with increased total costs of 1013 pounds sterlings- 2564 pounds sterlings/patient, giving incremental cost-effectiveness ratios of 4508 pounds sterlings: 15,515 pounds sterlings/QALY gained, well within current UK willingness-to-pay limits. Results were robust under a wide range of plausible assumptions. CONCLUSIONS: Based on the moderate level of clinical evidence available to date, improvements in glycaemic control with interventions, including SMBG, can improve patient outcomes, with acceptable cost-effectiveness ratios in the UK setting.

Blood Glucose Self-Monitoring↗
PubMed2006

The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy.

INTRODUCTION: The RENAAL (Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that, in hypertensive patients with type 2 diabetes mellitus and nephropathy, treatment with losartan plus conventional antihypertensive therapy (CT) reduced the relative risk of end-stage renal disease (ESRD) by 29% versus placebo over the time span of the study (mean patient follow-up of 3.4 years). The objective of this study was to project the effect of losartan compared with placebo on the lifetime incidence of ESRD and associated costs (from a US healthcare system perspective). METHODS: To estimate lifetime incidence of ESRD, we used a competing risks method to account for the risk of death without ESRD. We estimated the cost (US dollars, year 2002 values) associated with ESRD by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD, the cost of losartan study therapy and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Costs and outcomes were discounted by 3% per annum. RESULTS: We projected a lower lifetime incidence of ESRD for losartan patients (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in cost associated with ESRD of US dollars 31,803 per patient and a gain of 0.99 life-years per patient (0.70 discounted). After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a lifetime net saving of US dollars 24,632 per patient. CONCLUSION: Treatment with losartan plus CT in patients with type 2 diabetes and nephropathy reduced the within-trial incidence of ESRD and is projected to result in lifetime reductions in ESRD and associated costs, and increased survival, versus placebo.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes.

The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (HbA(1c) [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed (<or=3 years), drug-naive, type 2 diabetic subjects (fasting plasma glucose <or=10 mmol/l), we examined a representative subgroup (n = 921) of the U.S. cohort in ADOPT (A Diabetes Outcome Progression Trial). The relationship between levels of CRP, fibrinogen, PAI-1 antigen and PAI-1 activity, and baseline variables including National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome phenotype were explored. All four factors increased significantly with increasing numbers of metabolic syndrome components (P = 0.0136 to P < 0.0001). BMI (P < 0.0001) and HOMA-IR (P < 0.0001) but not A1C (P = 0.65) increased with increasing numbers of metabolic syndrome components. Adjustment of CRP levels for BMI eliminated the association between CRP and the number of metabolic syndrome components, while adjusting for HOMA-IR did not (P = 0.0028). The relationships of PAI-1 antigen and PAI-1 activity with the number of metabolic syndrome components were maintained after adjusting for BMI (P = 0.0002 and P = <0.0001, respectively) or HOMA-IR (P = 0.0008 and P = <0.0001, respectively), whereas that with fibrinogen was eliminated after adjusting for BMI but not after adjusting for HOMA-IR (P = 0.013). Adjustment for A1C had no effect on any of the relationships between the inflammatory and fibrinolytic factors and the metabolic syndrome. We conclude that in recently diagnosed, drug-naive type 2 diabetic subjects, markers of inflammation and fibrinolysis are strongly related to the number of metabolic syndrome components. Further, for CRP and fibrinogen this relationship is determined by body adiposity and not by insulin sensitivity or glucose control.

Adiposity↗
PubMed2006

An evaluation of cost sharing to finance a diet and physical activity intervention to prevent diabetes.

OBJECTIVE: The Diabetes Prevention Program (DPP) lifestyle intervention is a cost-effective strategy to prevent type 2 diabetes, but it is unclear how this intervention could be financed. We explored whether this intervention could be offered in a way that allows return on investment for private health insurers while remaining attractive for consumers, employers, and Medicare. RESEARCH DESIGN AND METHODS: We used the DPP and other published reports to build a Markov simulation model to estimate the lifetime progression of disease, costs, and quality of life for adults with impaired glucose tolerance. The model assumed a health-payer perspective and compared DPP lifestyle and placebo interventions. Primary outcomes included cumulative incidence of diabetes, direct medical costs, quality-adjusted life-years (QALYs), and cost per QALY gained. RESULTS: Compared with placebo, providing the lifestyle intervention at age 50 years could prevent 37% of new cases of diabetes before age 65, at a cost of $1,288 per QALY gained. A private payer could reimburse $655 (24%) of the $2,715 in total discounted intervention costs during the first 3 intervention years and still recover all of these costs in the form of medical costs avoided. If Medicare paid up to $2,136 in intervention costs over the 15-year period before participants reached age 65, it could recover those costs in the form of future medical costs avoided beginning at age 65. CONCLUSIONS: Cost-sharing strategies to offer the DPP lifestyle intervention for eligible people between ages 50 and 64 could provide financial return on investment for private payers and long-term benefits for Medicare.

Aged↗
PubMed2006

Who is tested for diabetic kidney disease and who initiates treatment? The Translating Research Into Action For Diabetes (TRIAD) Study.

OBJECTIVE: We examined factors associated with screening for albuminuria and initiation of ACE inhibitor or angiotensin receptor blocker (ARB) treatment in diabetic patients. RESEARCH DESIGN AND METHODS: We conducted surveys and medical record reviews for 5,378 patients participating in a study of diabetes care in managed care at baseline (2000-2001) and follow-up (2002-2003). Factors associated with testing for albuminuria were examined in cross-sectional analysis at baseline. Factors associated with initiating ACE inhibitor/ARB therapy were determined prospectively. RESULTS: At baseline, 52% of patients not receiving ACE inhibitor/ARB therapy and without known diabetic kidney disease (DKD) were screened for albuminuria. Patients > or =65 years of age, those with higher HbA(1c), those with cardiovascular disease (CVD), and those without hyperlipidemia were less likely to be screened. Of the patients with positive screening tests, 47% began ACE inhibitor/ARB therapy. Initiation of therapy was associated with positive screening test results, BMI > or =25 kg/m(2), treatment with insulin or oral antidiabetic agents, peripheral neuropathy, systolic blood pressure > or =140 mmHg, and CVD. Of the patients receiving ACE inhibitor/ARB therapy or with known DKD, 63% were tested for albuminuria. CONCLUSIONS: Screening for albuminuria was inadequate, especially in older patients or those with competing medical concerns. The value of screening could be increased if more patients with positive screening tests initiated ACE inhibitor/ARB therapy. The efficiency of screening could be improved by limiting screening to diabetic patients not receiving ACE inhibitor/ARB therapy and without known DKD.

Albuminuria↗
PubMed2006

Prevalence and determinants of insulin resistance among U.S. adolescents: a population-based study.

OBJECTIVE: We sought to examine the distribution of insulin and homeostasis model assessment of insulin resistance (HOMA-IR) and associations of HOMA-IR with sex, race/ethnicity, age, and weight status, as measured by BMI, among U.S. adolescents. RESEARCH DESIGN AND METHODS: Of 4,902 adolescents aged 12-19 years who participated in the National Health and Nutrition Examination Survey 1999-2002, analysis was performed for a nationally representative subsample of 1,802 adolescents without diabetes who had fasting laboratory measurements. The main outcome measure was HOMA-IR, calculated from fasting insulin and glucose and log transformed for multiple linear regression analyses. RESULTS: In adjusted regression models that included age and weight status, girls had higher HOMA-IR than boys and Mexican-American children had higher HOMA-IR levels than white children. There were no significant differences in adjusted HOMA-IR between black and white children. Obese children (BMI >/=95th percentile) had significantly higher levels of HOMA-IR compared with children of normal weight (BMI <85th percentile) in adjusted comparisons (mean HOMA-IR 4.93 [95% CI 4.56-5.35] vs. 2.30 [2.21-2.39], respectively). Weight status was by far the most important determinant of insulin resistance, accounting for 29.1% of the variance in HOMA-IR. The prevalence of insulin resistance in obese adolescents was 52.1% (95% CI 44.5-59.8). CONCLUSIONS: Obesity in U.S. adolescents represents the most important risk factor for insulin resistance, independent of sex, age, or race/ethnicity. The prevalence of insulin resistance in obese children foreshadows a worrisome trend for the burden of type 2 diabetes in the U.S.

Adolescent↗
PubMed2006

Impact of active versus usual algorithmic titration of basal insulin and point-of-care versus laboratory measurement of HbA1c on glycemic control in patients with type 2 diabetes: the Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) trial.

OBJECTIVE: The objective of this study was to assess the impact of active versus usual monitoring of algorithmic insulin titration and point-of-care (POC) versus laboratory HbA1c (A1C) measurement on glycemic control in primary care. RESEARCH DESIGN AND METHODS: The Glycemic Optimization with Algorithms and Labs at Point of Care (GOAL A1C) study was a 24-week, randomized, parallel-group, four-arm, open-label study of 7,893 adults with type 2 diabetes uncontrolled by oral antidiabetic agents and requiring insulin. Patients were randomly assigned by investigators from 2,164 sites in the U.S. to insulin glargine with either 1) usual (no unsolicited contact between visits) insulin titration using a simple algorithm with laboratory A1C testing, 2) usual titration with POC A1C testing, 3) active (weekly monitored) titration with laboratory A1C testing, or 4) active titration with POC A1C testing. Outcome measures included a change in A1C and fasting self-monitoring of blood glucose (SMBG) levels, percentage of patients achieving A1C <7.0%, and hypoglycemia frequency. RESULTS: Significant A1C and SMBG reductions were observed in all arms (P < 0.0001). Compared with usual insulin titration, active titration achieved greater A1C reduction (1.5 vs. 1.3%; P < 0.0001), SMBG reduction (88 vs. 79 mg/dl; P < 0.0001), and proportion of patients achieving A1C <7.0% (38 vs. 30%; P < 0.0001). Among patients receiving active titration, POC A1C testing was associated with an increase in the proportion achieving an A1C <7.0% (41% for POC vs. 36% for laboratory; P < 0.0001). Hypoglycemia rates were low (usual vs. active groups: 3.7 vs. 6.0 all confirmed episodes/patient-year [P < 0.001]; 0.09 vs. 0.14 severe episodes/patient-year [NS]). CONCLUSIONS: In a predominantly primary care setting, addition of insulin glargine using a simple algorithm achieved significant improvements in glycemic control in patients with type 2 diabetes in all four study arms. Active titration resulted in significant incremental improvements in glycemic control, and, among patients receiving active titration, POC A1C testing resulted in a greater portion achieving A1C <7.0%.

Administration, Oral↗
PubMed2006

Diabetes reporting as a cause of death: results from the Translating Research Into Action for Diabetes (TRIAD) study.

OBJECTIVE: To determine the frequency of reporting of diabetes on death certificates of decedents with known diabetes, define factors associated with reporting of diabetes, and describe trends in reporting over time. RESEARCH DESIGN AND METHODS: Data were obtained from 11,927 participants with diabetes who were enrolled in the Translating Research Into Action for Diabetes study, a multicenter prospective observational study of diabetes care in managed care. Data on decedents (n = 540) were obtained from the National Death Index. The primary dependent variable was the presence of ICD-10 codes for diabetes on the death certificate. Covariates included age at death, sex, race/ethnicity, education, income, duration of diabetes, type of diabetes, diabetes treatment, smoking status, and number of comorbidities. RESULTS: Diabetes was recorded on 39% of death certificates and as the underlying cause of death for 10% of decedents with diabetes. Diabetes was significantly less likely to be reported on the death certificates of decedents with diabetes dying of cancer. Predictors of recording diabetes anywhere on the death certificate included longer duration of diabetes and insulin treatment. Longer duration of diabetes, insulin treatment, and fewer comorbidities were associated with recording of diabetes as the underlying cause of death. CONCLUSIONS: Diabetes is much more likely to be reported on the death certificates of diabetic individuals who die of cardiovascular causes. Reporting of diabetes on death certificates has been stable over time. Death certificates underestimate the prevalence of diabetes among decedents and present a biased picture of the causes of death among people with diabetes.

Cause of Death↗
PubMed2006

Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion.

OBJECTIVE: To evaluate the impact of prior intensive diabetes therapy on neuropathy among former Diabetes Control and Complications Trial (DCCT) participants. RESEARCH DESIGN AND METHODS: At the conclusion of the DCCT, subjects in the intensive group were encouraged to maintain intensive therapy, and subjects in the conventional group were encouraged to begin intensive therapy. Thereafter, we annually assessed neuropathy as part of the Epidemiology of Diabetes Intervention and Complications (EDIC) study. Neuropathy was defined using the Michigan Neuropathy Screening Instrument (MNSI). We recorded potential adverse consequences of neuropathy. RESULTS: At the first EDIC examination, 1,257 subjects participated in the neuropathy assessment. Consistent with DCCT results, the former intensive group showed a lower prevalence of neuropathy than the conventional group based on positive questionnaire (1.8 vs. 4.7%; P = 0.003) or examination (17.8 vs. 28.0%; P < 0.0001) results. Despite similar levels of glycemic control, symptoms and signs of neuropathy remained less prevalent among the former intensive group compared with the conventional group. At the beginning of the EDIC study, prior intensive therapy reduced the odds of having symptoms and signs of neuropathy using MNSI criteria by 64% (P = 0.0044) and 45% (P < 0.0001), respectively, with similar odds reductions observed for both neuropathic symptoms (51%, P < 0.0001) and neuropathic signs (43%, P < 0.0001) across 8 years of EDIC follow-up. CONCLUSIONS: The benefits of 6.5 years of intensive therapy on neuropathy status extended for at least 8 years beyond the end of the DCCT, similar to the findings described for diabetic retinopathy and nephropathy.

Diabetes Mellitus, Type 1↗