Long-term Absolute Risk for Cardiovascular Disease Stratified by Fasting Glucose Level.

OBJECTIVE: To estimate the long-term absolute risk for cardiovascular disease (CVD) according to fasting glucose (FG) levels below the threshold of diabetes. RESEARCH DESIGN AND METHODS: We pooled data from seven observational cohorts of U.S. black and white men and women followed from 1960 to 2015. We categorized FG as follows: <5.0, 5.0-5.5, 5.6-6.2, 6.3-6.9 mmol/L, and diabetes (FG ≥7.0 mmol/L or use of diabetes medications). CVD was defined as fatal/nonfatal coronary heart disease and fatal/nonfatal stroke. We estimated the risk of CVD by FG category at index age 55 years using a modified Kaplan-Meier survival analysis, adjusted for the competing risk of non-CVD death. We also assessed risk for incident CVD according to change in FG before 50 years of age, specifically among the categories <5.6 mmol/L, 5.6-6.9 mmol/L, and diabetes. RESULTS: Our sample included 19,630 individuals (6,197 blacks and 11,015 women) without a prior CVD event. Risk for CVD through 85 years of age ranged from 15.3% (<5.0 mmol/L) to 38.6% (diabetes levels) among women and from 21.5% (5.0-5.5 mmol/L) to 47.7% (diabetes levels) among men. An FG of 6.3-6.9 mmol/L was associated with higher long-term CVD risk compared with the lowest FG among men but not women. Increases in glucose during midlife with conversion to diabetes were associated with higher cardiovascular risk (1.3- to 3.6-fold) than increases in glucose below the diabetes threshold. CONCLUSIONS: Middle-age individuals with diabetes have high long-term absolute risk for CVD. These data strongly support the importance of blood glucose monitoring in midlife for CVD prevention.

Prevalence of micro- and macrovascular diabetes complications at time of type 2 diabetes diagnosis and associated clinical characteristics: A cross-sectional baseline study of 6958 patients in the Danish DD2 cohort.

AIMS: To examine the prevalence of micro- and macrovascular complications and their associated clinical characteristics at time of type 2 diabetes (T2D) diagnosis. METHODS: We examined the prevalence of complications and associated clinical characteristics among 6958 newly diagnosed T2D patients enrolled in the prospective Danish Center for Strategic Research in T2D cohort during 2010-2016. We calculated age- and gender-adjusted prevalence ratios (aPRs) of complications using log-binomial and Poisson regression. RESULTS: In total, 35% (n=2456) T2D patients had diabetic complications around diagnosis; 12% (n=828) had microvascular complications, 17% (n=1186) macrovascular complications, and 6% (n=442) had both. HbA1c levels of ≥7% were associated with microvascular complications [HbA1c 7%-8%; aPR: 1.35, 95% confidence interval (CI): 1.12-1.62] but not macrovascular complications [aPR: 0.91, 95% CI: 0.76-1.08]. High C-peptide≥800pmol/L was associated with macrovascular [aPR 1.34, 95% CI: 1.00-1.80] but not microvascular [aPR 0.97, 95% CI: 0.71-1.33] complications. Macrovascular complications were associated with male sex, age>50years, obesity, hypertriglyceridemia, low HDL cholesterol, smoking, elevated CRP levels, and anti-hypertensive therapy. Microvascular complications were associated with high blood pressure, hypertriglyceridemia, and absence of lipid-lowering therapy. CONCLUSIONS: One-third of patients with T2D had diabetes complications around time of diagnosis. Our findings suggest different pathophysiological mechanisms behind micro- and macrovascular complications.

Association of Diabetes and Prognosis of Minor Stroke and Its Subtypes: A Prospective Observational Study.

BACKGROUND: The association between diabetes mellitus (DM) and prognosis of minor stroke is unclear. The aim of this study is to investigate whether DM contributes to the prognosis of minor stroke or its specific subtype. METHODS: All minor ischemic stroke patients were derived from the China National Stroke Registry and classified into 5 subtypes according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. DM was defined as either self-reported physician diagnosis of diabetes or use of hypoglycemic medications during hospitalization or at discharge. Patients were followed up for 1 year for clinical outcomes of recurrent stroke, death and functional outcome. Poor functional outcomes were defined as a score of 2-6 for modified Rankin Score. Associations between DM and prognosis of minor stroke and its subtypes were analyzed by univariable and multivariable logistic regression. RESULTS: Of 4,548 patients with minor stroke, 1,230(27.0%) patients had DM, 1,038(22.8%) had poor outcomes and 570(13.0%) of 4,401 patients had recurrent stroke at 1 year. In multivariable analyses, DM were significantly associated with 1-year stroke recurrence (Odds Ratio [OR], 1.31; 95% confidence interval [CI]: 1.08-1.59) and poor outcome (OR, 1.51; 95%CI: 1.28-1.77). Among the subtypes of minor stroke, DM was only significantly associated with 1-year stroke recurrence (OR, 1.63; 95%CI: 1.07-2.50) and poor outcome (OR, 1.73; 95%CI: 1.22-2.45) in the small-artery occlusion subtype. CONCLUSIONS: DM significantly increased the risk of stroke recurrence and poor outcome in the small-artery occlusion subtype, but not in other subtypes of minor stroke.

Progress on diabetic cerebrovascular diseases.

Diabetic cerebrovascular diseases are defined as cerebral vascular diseases induced by diabetes with sugar, fat and a series of nutrient substance metabolic disorders, resulting in intracranial large and small vessel diseases. About 20%-40% patients with type 2 diabetes suffer from cerebral blood vessel diseases. Diabetic cerebrovascular diseases are the main causes of death in patients with diabetes mellitus. The major clinical manifestations are asymptomatic cerebral atherosclerosis, stroke, cerebral small vessel disease and acute cerebral vascular disease. The pathogenesis, clinical characteristics, treatment and prognosis of diabetic cerebrovascular disease are obviously different from non-diabetic cerebral vascular diseases. This paper will focus on the diabetic cerebrovascular disease, including its latest research progress. Diabetic cerebral large vascular disease and diabetic cerebral small vessel disease will be reviewed here.

[Heterogenicity of type 2 diabetes mellitus: clinical characteristics of 4 subtypes].

AIM: To characterize clinically subtypes of type 2 diabetes mellitus (DM2) depending on lymphocyte reaction to insulin. MATERIAL AND METHODS: DM2 patients (n = 357) were divided into 4 groups: DM2a - direct response of lymphocytes to insulin (RLI) detected in lymphocyte blast transformation reaction, ICA+; DM2b - indirect RLI detected at inhibition of cells with receptors to histamine with cimetidin, ICA+; DM2c -indirect RLI detected at inhibition of cells synthetizing prostaglandin with indometacine, ICA-; DM2d - the absence of RLI, ICA-. RESULTS: DM2a patients were characterized by 5-year need in insulin, development of microangiopathy. DM2b patients - by overweight, combination of micro- and macroangiopathy, high risk of stroke, myocardial infarction, diabetic foot, need in insulin. DM2c patients had classic DM2, they were not in need of insulin at early stages of the disease, with typical development of macroangiopathy. DM2d patients had pancreatogenic DM. CONCLUSION: Application of the immunological criterion (type of RLI) differentiates DM2 patients with different course, prognosis. They need different treatment.

Incidence and development of diabetic microangiopathy of fulminant type 1 diabetes--comparison with non-fulminant type 1 diabetes.

OBJECTIVE: The data from the Fulminant Type 1 Diabetes Committee suggested that patients with fulminant type 1 diabetes are a subgroup at high risk for diabetic microangiopathy in the first 5 years after diagnosis associated with the lack of endogenous insulin secretion from the onset of diabetes. The aim of this study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes followed in our diabetes center. METHODS: Sixteen patients with fulminant type 1 diabetes and 60 age-matched patients with non-fulminant type 1 diabetes were recruited as subjects. The existence or lack of diabetic retinopathy and nephropathy, average HbA(1C) level, serum C-peptide level, average blood pressure, insulin level, whether or not they were taking antihypertensive agents, and smoking history were investigated retrospectively based on medical records. RESULTS: The 5-year incidence of microangiopathy was lower in fulminant than in non-fulminant type 1 diabetes patients; retinopathy cases occurred in 0% vs. 8.3% of patients, and nephropathy occurred in 0% vs. 1.7% of patients. The 10-year incidence of retinopathy was 0% vs. 24.1%, and that of nephropathy was 11.1% vs. 3.4%. The cumulative incidence of microangiopathy did not differ between the fulminant and non-fulminant type 1 diabetes patients. Mean HbA(1C) levels and systolic blood pressure were significantly lower in fulminant type 1 diabetes patients. CONCLUSION: No difference between the patients visiting the center with fulminant type 1 diabetes and those with non-fulminant type 1 diabetes was observed in the development of microangiopathy complications.

Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus-The STOP-NIDDM risk-score.

AIMS: To develop a risk-score model, based on available clinical data to assess absolute risk of type 2 diabetes among people with impaired glucose tolerance (IGT). METHODS: Data from the study to prevent non-insulin dependent diabetes mellitus (STOP-NIDDM) investigating acarbose treatment in individuals with IGT were used to develop multivariable Cox proportional hazards model for the time to onset of diabetes. The final model equation was externally validated using data from the Finnish Cardiovascular Risk Factor (FINRISK) population. RESULTS: The risk-score model included the variables acarbose treatment, gender, serum triglyceride level, waist circumference, fasting plasma glucose, height, history of cardiovascular disease (CVD) and hypertension. The final model yielded an area under the receiver-operating-characteristic curve (AUC(ROC)) of 0.64 when applied to people with IGT in the STOP-NIDDM, and 0.84 and 0.90 when applied to FINRISK population with IGT alone and IGT and normal glucose tolerance combined, respectively; AUC(ROC) is a measure of the discriminatory power of the model (1, perfect discrimination). CONCLUSIONS: The STOP-NIDDM risk-score is a simple and validated tool that can identify high-risk individuals with IGT who would benefit most from type 2 diabetes or CVD prevention strategies, such as lifestyle management or early acarbose treatment.

Longitudinal change in HbA1c in patients with type 2 diabetes: comparison of short-acting, biphasic and basal insulin.

OBJECTIVE: To evaluate the annual change in HbA1c values among patients with type 2 diabetes in primary care practices comparing different insulin regimens. RESEARCH DESIGN AND METHODS: Longitudinal data from 666 nationwide general and internal medicine practices in Germany (Disease Analyser, IMS HEALTH) from 7/2004 to 6/2006 were analysed, including 348 patients (mean age+/-SD: 61+/-11 years) with continuous short-acting (regular insulin or analogues), 1 906 with biphasic (72+/-9 years), 439 with basal-bolus (68+/-10 years), and 1 719 with basal insulin therapy (65+/-10 years). The mean of the individual relative changes in HbA1c (level in 2006 divided by level in 2005) were compared between insulin groups, adjusting for age, sex, BMI, diabetes duration, oral antidiabetics, comorbidity, health insurance, visits, hospitalisations, and practice type using general linear models. RESULTS: There was only a small difference in baseline HbA1c values (range 7.3-7.5%) between the four insulin groups (p=0.008). Substantial group differences were observed for age, diabetes duration, and additional prescriptions of oral antidiabetics (p<0.0001). After adjusting for potential confounders, the relative annual increase in HbA1c was highest for biphasic insulin (1.021; 95%CI 1.016-1.025), followed by basal-bolus therapy (1.017; 1.012-1.022), and basal insulin (monotherapy) (1.012; 1.002-1.021). No significant change in HbA1c was found for short-acting insulin (1.006; 0.996-1.016). CONCLUSIONS: Although many options for insulin therapy are now available, a progression of glycemia still occurs in the majority of insulin-treated type 2 diabetic patients in primary care.

Use of the SINBAD classification system and score in comparing outcome of foot ulcer management on three continents.

OBJECTIVE: To compare populations with and outcomes of diabetic foot ulcers managed in the U.K., Germany, Tanzania, and Pakistan and to explore the use of a new score of ulcer type in comparing outcomes among different countries. RESEARCH DESIGN AND METHODS: Data from a series of 449 patients with diabetic foot ulcers managed in the U.K. were used to evaluate the new simplified system of classification and to derive an aggregate score. The use of the score was then explored using data from series managed in Germany (n = 239), Tanzania (n = 479), and Pakistan (n = 173). RESULTS: A highly significant difference was found in time to healing between ulcers of increasing score in the U.K. series (Kruskal-Wallis test; P = 0). When data from all centers were examined, a step-up in days to healing was noted for those with scores of >or=3 (out of 6). Examination of baseline variables contributing to outcome revealed the following differences among centers: ischemia, ulcer area, and depth contributing to outcome in the U.K.; ischemia, area, depth, and infection in Germany; depth, infection, and neuropathy in Tanzania; and depth alone in Pakistan. CONCLUSIONS: Any system of classification designed for general implementation must encompass all the variables that contribute to outcome in different communities. Adoption of a simple score based on these variables, the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) score, may prove useful in predicting ulcer outcome and enabling comparison among different centers.

Hemorheologic changes in type 2 diabetic patients with microangiopathic skin lesions. A linear discriminant categorizing analysis.

The development of diabetic microangiopathy may produce lesions in distinct organic territories (the skin, among others). With an intention of identifying hemorheologic variables for a better characterization of diabetic patients, we studied plasmatic and blood viscosities (P Visc at 2.30 s(-1) and B Visc at 4.60 and 230 s(-1)), fibrinogenemia, and erythrocytic aggregation in 40 type 2 diabetic patients (13 with microangiopathic skin lesions and 27 without) and in 30 healthy controls. Considering its alterations in diabetic patients and applying linear discriminant analysis, two models may be characterized: (a) discriminant function (Disc F)=0.58 aggregate shape parameter (ASP)-0.61 B Visc(230)+0.89 fibrinogenemia for discriminating healthy individuals from diabetic patients with microangiopathic skin lesions and (b) Disc F=6.325 ASP-0.347 B Visc(230)+0.013 fibrinogenemia for discriminating healthy controls from diabetic patients with and without microangiopathic skin lesions. Both models appear to be valid due to the following: (a) Model 1: a coefficient of canonic correlation of 0.924, a highly significant Mahalanobis distance (P<10(-3)), a correct percentage of classification (100%), and the centroids of each group (0.94 and 5.63); (b) Model 2: a coefficient of canonic correlation of 0.898, a highly significant Mahalanobis distance (P<10(-3)), a correct percentage of classification (85.7%), and the centroids of each group (-1.9, 1.9, and 2.4). Just as the alterations in the analyzed hemorheologic variables could be suggesting their possible involvement in the physiopathogenia of diabetic microangiopathic skin lesions, the proposed models could characterize a microcirculatory profile in diabetic patients for preventing irreversible damages.

Spectrum of autonomic cardiovascular neuropathy in diabetes.

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.

Effectiveness of the diabetic foot risk classification system of the International Working Group on the Diabetic Foot.

OBJECTIVE: To evaluate the effectiveness of a diabetic foot risk classification system by the International Working Group on the Diabetic Foot to predict clinical outcomes. RESEARCH DESIGN AND METHODS: A total of 225 diabetic patients were initially evaluated as part of a prospective case-control study at the University of Texas Health Science Center at San Antonio. Complete records were available for 213 patients for follow-up evaluation after 29 months. Upon enrollment, subjects were stratified into four risk groups based on the presence of risk factors according to the consensus of the International Working Group on the Diabetic Foot. Group 0 consisted of subjects without neuropathy, group 1 consisted of patients with neuropathy but without deformity or peripheral vascular disease (PVD), group 2 consisted of subjects with neuropathy and deformity or PVD, and group 3 consisted of patients with a history of foot ulceration or a lower-extremity amputation. RESULTS: Upon enrollment, patients in higher-risk groups had longer duration of diabetes, worse glycemic control, vascular and neuropathic variables, and more systemic complications of diabetes. During 3 years of follow-up, ulceration occurred in 5.1, 14.3, 18.8, and 55.8% of the patients in groups 0, 1, 2, and 3, respectively (linear-by-linear association, P < 0.001). All amputations were found in Groups 2 and 3 (3.1 and 20.9%, P < 0.001). CONCLUSIONS: The foot risk classification of the International Working Group on the Diabetic Foot predicts ulceration and amputation and can function as a tool to prevent lower-extremity complications of diabetes.

[Importance of lower limbs diabetic angioneuropathy classification ]. / Klassifikatsiia diabeticheskoi angioneiropatii nizhnikh konechnostei.

The author proposes classification which determines continuity in the treatment of patients with lower limbs diabetic angioneuropathy. In working classification the stage of disease (compensation, decompensation), form (with or without major circulation disorder), type (complicated, uncomplicated) are taken into account. The proposed classification solves tactical, diagnostic and curative problems. This permitted to decrease the rate of amputations from 32 to 5.7% and lethality from 15 to 3.5%.

Changes in frequency and severity of limited joint mobility in children with type 1 diabetes mellitus between 1976-78 and 1998.

OBJECTIVE: Limited joint mobility (LJM), the earliest clinically apparent long-term complication of type 1 diabetes mellitus, is a risk indicator for microvascular complications, and its appearance is primarily affected by long-term metabolic control. We hypothesized that the prevalence of LJM had decreased during the past 20 years. STUDY DESIGN: We examined 312 subjects with type 1 diabetes mellitus, aged 7 to 18 years, using the same examination method and criteria as in studies of 515 subjects in this age group carried out between 1976 and 1978 for whom primary data were available, including age, duration of diabetes, and LJM stage. Statistical analyses included exact chi(2) tests, independent sample t tests, and unconditional logistic regression. RESULTS: There was a >4-fold reduction in frequency of LJM between 1976-78 and 1998 (31% vs 7%, P <.001), with a decrease in the proportion having moderate or severe LJM (35% vs 9%, P =.025). CONCLUSIONS: These findings confirm the hypothesis that the prevalence of LJM has decreased, most likely the result of improved blood glucose control during the past 2 decades.

[The impact of dipper and non-dipper characteristics in the fluctuation of arterial blood pressure. A study of a population of 484 diabetic patients]. / Les conséquences du caractère dipper et non dipper de la courbe de pression artérielle. Etude d'une population de 484 patients diabétiques.

Abnormal pattern of circadian blood pressure variations carries a high risk of cardiovascular complications. The aim of this study was to assess the frequency of abnormal blood pressure rhythm in diabetes and its consequences on micro and macrovascular complications. 484 diabetes mellitus patients were submitted to 24-h ambulatory blood pressure monitoring. They were divided into two groups according to the absence (non-dipper: group 1; n = 167) or presence (dipper: group 2; n = 317) of nocturnal BP reduction = 10% of daytime BP. Following data were collected and compared between these two groups: body mass index, glycated haemoglobin, urinary albumin excretion, research of retinopathy by fundoscopy, tests for presence of a macrovascular disease. There were no significant differences among the two groups in sex, body mass index, type and duration of diabetes and glycemic control. Clinical SBP and DBP did not differ from significant manner between non-dipper and dipper (140 +/- 18/81 +/- 1 versus 138 +/- 19/81 +/- 10 mmHg). Non-dipper 24-h SBP and 24-h DBP were higher than those of dipper (129 +/- 16/76 +/- 9 versus 122 +/- 15/73 +/- 8 mmHg; p < 0.001). Non-dipper were older than dipper (59.9 +/- 13 versus 55.8 +/- 15 years; p < 0.001) and there was more hypertensive patients in group 1 than in group 2 (50% versus 39%; p < 0.01). Macro- and microvascular diabetes complications were more common in non-dipper. In conclusion high blood pressure is frequently observed in diabetic patients. Its association with a diminished nocturnal BP fall could explain a higher risk of complications, especially retinopathy, nephropathy and cardiac events.

Case complexity and clinical outcome in diabetes mellitus. A prospective study using the INTERMED.

The aim of this study was to assess a population of patients with diabetes mellitus by means of the INTERMED, a classification system for case complexity integrating biological, psychosocial and health care related aspects of disease. The main hypothesis was that the INTERMED would identify distinct clusters of patients with different degrees of case complexity and different clinical outcomes. Patients (n=61) referred to a tertiary reference care centre were evaluated with the INTERMED and followed 9 months for HbA1c values and 6 months for health care utilisation. Cluster analysis revealed two clusters: cluster 1 (62%) consisting of complex patients with high INTERMED scores and cluster 2 (38%) consisting of less complex patients with lower INTERMED. Cluster 1 patients showed significantly higher HbA1c values and a tendency for increased health care utilisation. Total INTERMED scores were significantly related to HbA1c and explained 21% of its variance. In conclusion, different clusters of patients with different degrees of case complexity were identified by the INTERMED, allowing the detection of highly complex patients at risk for poor diabetes control. The INTERMED therefore provides an objective basis for clinical and scientific progress in diabetes mellitus. Ongoing intervention studies will have to confirm these preliminary data and to evaluate if management strategies based on the INTERMED profiles will improve outcomes.