Palumbo, Pasquale J

Glycemic management is central in prevention of small vessel and cardiovascular complications in type 2 diabetes. With the plethora of newer medications and recommendations for a patient centered approach, more information is necessary to match the proper drug to each patient. We showed that BARI 2D, a five-year trial designed to compare two different glycemic treatment strategies, was suitable for assessing different responses according to different phenotypic characteristics. Treatment with insulin sensitizing medications such as thiazolidinediones and metformin was more effective in improving glycemic control, particularly in the more insulin resistant patient, when compared to the insulin provision strategy using insulin and or sulfonylureas. Triglyceride and high density lipoprotein ratio (TG/HDL-cholesterol ratio) was found to be a readily available and practical biomarker that helps to identify the insulin resistant patient. These results support the concept that not all medications for glycemic control work the same in all patients. Thus, tailored therapy can be done using phenotypic characteristics rather than a “one-size-fits-all approach.”

Background Our previous study of nonelderly adult decedents with nonnatural (accident, suicide, or homicide) cause of death (96% autopsy rate) between 1981 and 2004 revealed that the decline in subclinical coronary artery disease ( CAD ) ended in the mid‐1990s. The present study investigated the contributions of trends in obesity and diabetes mellitus to patterns of subclinical CAD and explored whether the end of the decline in CAD persisted. Methods and Results We reviewed provider‐linked medical records for all residents of Olmsted County, Minnesota , who died from nonnatural causes within the age range of 16 to 64 years between 1981 and 2009 and who had CAD graded at autopsy. We estimated trends in CAD risk factors including age, sex, systolic blood pressure, diabetes (qualifying fasting glucose or medication), body mass index, smoking, and diagnosed hyperlipidemia. Using multiple regression, we tested for significant associations between trends in CAD risk factors and CAD grade and assessed the contribution of trends in diabetes and obesity to CAD trends. The 545 autopsied decedents with recorded CAD grade exhibited significant declines between 1981 and 2009 in systolic blood pressure and smoking and significant increases in blood pressure medication, diabetes, and body mass index ≥30 kg/m 2 . An overall decline in CAD grade between 1981 and 2009 was nonlinear and ended in 1994. Trends in obesity and diabetes contributed to the end of CAD decline. Conclusions Despite continued reductions in smoking and blood pressure values, the previously observed end to the decline in subclinical CAD among nonelderly adult decedents was apparent through 2009, corresponding with increasing obesity and diabetes in that population.

Insulin binding by insulin antibodies was determined serially in eight menstruating and in twelve pregnant diabetic subjects. No significant variation was noted in the insulin binding values before, during or after menstruation or during or after pregnancy. This constancy of insulin binding was observed despite major and minor changes in insulin needs. No causal relationship could be demonstrated between insulin binding by insulin antibodies and changing insulin requirements. If there is a relationship between the hormonal changes and the alterations in insulin needs during menstruation and pregnancy, the mechanism of this relationship is not mediated through the insulin binding capacity of circulating insulin antibodies.

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 < .01); older age at onset of diabetes (P < .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.

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.

OBJECTIVEThe Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN).RESEARCH DESIGN AND METHODSDPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score >2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates.RESULTSResults are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62 ± 9 years, mean HbA1c 7.7 ± 1.6%, diabetes duration 10 ± 9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P = 0.02), which remained significant after adjusting for the in-trial HbA1c (P = 0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58–0.99], P < 0.01).CONCLUSIONSAmong patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

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.