Long-term influence of type 2 diabetes and metabolic syndrome on all-cause and cardiovascular death, and microvascular and macrovascular complications in Chinese adults — A 30-year follow-up of the Da Qing diabetes study

To determine the prevalence of vascular complications among inpatients with type 2 diabetes mellitus (T2DM) and factors independently associated with vascular complications in a tertiary care department in Ningbo, China, the authors conducted a cross-sectional study using an existing computerised medical records database. A total of 3370 adult patients with T2DM were admitted to this tertiary care department for the first time between 2012 and 2017. Patients were categorised as those (1) with at least one vascular complication, (2) with at least one microvascular complication, and (3) with at least one macrovascular complication. Over 5 years, the prevalence of vascular, microvascular, and macrovascular complications among inpatients with T2DM was 73.2%, 57.5%, and 51.4%, respectively. The odds of vascular, microvascular, and macrovascular complications increased with age and were higher in patients with hypertension. The odds of vascular and microvascular complications were higher in single, divorced, or widowed patients, patients with T2DM for a long time, and patients on advanced T2DM therapeutic regimen. The odds of vascular and macrovascular complications were lower in women. The odds of microvascular complications decreased with education. The odds of macrovascular complications were higher in smokers. In conclusion, in the tertiary care department, more than half of inpatients with T2DM had vascular complications, and factors independently associated with vascular complications were identified. The study findings could be used in future interventional studies to prevent and manage vascular complications among these patients.

The predictive value of Thromboelastography (TEG) parameters in vascular complications in patients with type 2 diabetes mellitus

Background:The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.Methods:We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.Results:In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. The duration of T2DM also significantly associated with the prevalence of “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. Subsequently, the prevalence of “disturbances of pigmentation” was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of “disturbances of pigmentation” was also significant in NGT and T2DM groups (P < 0.01).Conclusions:There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Targets for Glycemic Control

A comparative study of the clinical profile of fibrocalculous pancreatic diabetes and type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) in children and adolescents is becoming an increasingly important public health concern throughout the world (1–17). Because of the relatively recent recognition of the problem in this age group, many children with new onset T2DM may be misclassified as having T1DM. Conversely, as the population becomes heavier, overweight adolescents with autoimmune diabetes may be misdiagnosed as having T2DM. T2DM is often associated with risk factors for cardiovascular disease that may already be present at the time of diagnosis, making normalization of blood glucose levels and diagnosis and treatment of hypertension and dyslipidemia important (18). T2DM occurs when insulin secretion is inadequate to meet the increased demand posed by insulin resistance (19). Thus, T2DM is commonly associated with other features of the insulin resistance syndrome [hyperlipidemia, hypertension, acanthosis nigricans, ovarian hyperandrogenism, non-alcoholic fatty liver disease (NAFLD)] (20). Insulin secretion depends on disease status and duration, and can vary from delayed but markedly elevated in response to a glucose challenge, to absolutely diminished (19). Adults with symptoms have 50% reduction at the time of diagnosis, and may become insulin dependent within a few years (21). T2DM occurs: in youth most often during the second decade of life, with a mean age of diagnosis of ∼13.5 years. This coincides with the peak of physiologic pubertal insulin resistance, which may lead to onset of overt diabetes in previously compensated adolescents. in all races, but at a much greater prevalence in those of non-white European descent, e.g. those of black African descent, native North American, Hispanic (especially Mexican)-American, Asian, South Asian (Indian Peninsula), and Native Pacific islanders. The SEARCH for Diabetes in Youth population-based study found the proportion of physician diagnosed T2DM among 10–19-year-olds to vary greatly by ethnicity in the US: 6% for non-Hispanic whites, 22% for Hispanics, 33% for blacks, 40% for Asians/Pacific Islanders, and 76% for Native Americans (8). In Hong Kong > 90% of young onset diabetes is T2DM (10), in Taiwan 50% (11) and nearly 60% in Japan (Ogawa et al. personal communication). in > 75% of cases in youth in the USA there is a first or second-degree relative with T2DM. in youth in the USA and Europe with body mass index (BMI) above 85th percentile for age and sex. In Japan, however, ∼30% of T2DM are not obese (17), in Asian Indian urban children, half of those with T2DM had normal weight (< 120% ideal for height) (12), and half of Taiwanese children with T2DM were not obese (11). in some asymptomatic individuals in high-risk populations during medical, school, or sports examinations (22,23). in the presence of ketosis/ketoacidosis, one third or more of newly diagnosed patients (24). This presentation is responsible for misclassification of T2DM patients as T1DM. occasionally with severe dehydration (hyperosmolar hyperglycemic coma, hypokalemia) at presentation, which can be fatal (24,25) with a sex ratio (male:female) that varies from 1: 4–1:6 in native North Americans to 1:1 in Asians and Libyan Arabs without associated HLA specificities. without associated islet cell autoimmunity (see autoimmunity T2DM). The pathophysiology of autoimmune 'T2DM' is unclear. It most likely represents autoimmune T1DM in overweight or obese individuals with underlying insulin resistance. It has been postulated that obesity and insulin resistance may promote an inflammatory response to antigen exposure caused by apoptosis of beta cells (26). Youth and adults in US and Europe who are clinically diagnosed with T2DM are found to have T1DM-associated auto-antibodies in 15–40% of cases, including many who are not receiving insulin one year after diagnosis (27–30). Antibody positive young adult individuals with the T2DM phenotype are significantly less overweight and younger than antibody negative patients (21, 27). Hemoglobin (HbA1c) concentrations are significantly higher in young adults with T2DM who are antibody positive compared with those who are antibody negative (27). ß-cell function is significantly less in antibody positive individuals, the most dramatic difference being reported in younger adult patients (25–34 years), resulting in more rapid development of insulin dependence, usually by 3 years duration (27, 30). The presence of islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies in adults with clinically typical T2DM has been referred to as latent autoimmune diabetes of adults (27, 31). Neither the autoimmunity nor the diabetes is latent, however (26). Atypical diabetes mellitus (ADM) occurs throughout childhood, but rarely begins past age 40. It has only been described in young people of African descent. There is a strong family history in multiple generations with an autosomal dominant pattern of inheritance, but an abnormal sex ratio (M : F = 1 : 3). ADM is not associated with HLA specificities and islet autoimmunity does not occur. Ketosis or ketoacidosis is typical at onset. Insulin secretion is present but diminished and without long-term deterioration of function. Interestingly, insulin is often not required for survival after treatment of acute metabolic deterioration, although diabetes control may be poor and ketoacidosis may recur without insulin, e.g. with illness or pregnancy. ADM is not associated with obesity beyond that in the general population and it is not associated with insulin resistance. Monogenic diabetes (formerly referred to as maturity onset diabetes of the young or MODY) For more in depth information see the ISPAD Clinical Consensus Guidelines for Monogenic Diabetes (34). Identified in families with multigenerational diabetes; including asymptomatic individuals identified through testing of family members. Monogenic diabetes is not associated with obesity beyond that in the general population and it is not associated with insulin resistance The clinician is obliged to weigh the evidence in each individual patient to distinguish between T1DM and T2DM. The reasons for this conundrum are: with increasing obesity in childhood, as many as 15–25% of newly diagnosed T1DM (or monogenic diabetes) patients may be obese. the significant number of pediatric patients with T2DM demonstrating ketonuria or ketoacidosis at diagnosis (2). T2DM is common in the general adult population, with a random family history of ∼15% or greater in minority populations, reducing the specificity of a positive family history. positive family history for T2DM is increased for patients with T1DM as much as threefold over the non-diabetic population and T1DM is more frequent in relatives of patients with T2DM (35, 36). There is considerable overlap in insulin or C-peptide measurements between T1DM, T2DM and MODY at onset of diabetes and over the first year or so. This overlap is due to the recovery phase of autoimmune-mediated T1DM (the honeymoon) and degree of glucotoxicity/lipotoxicity impairing insulin secretion at the time of testing in both T1DM and T2DM. In addition the insulin resistance of obesity raises residual C-peptide levels in obese adolescents with T1DM. Such measurements are thus relatively valueless in the acute phase. [The role of C peptide may be more helpful in established diabetes as persistent elevation of C-peptide above the level of normal would be unusual in T1DM after 12–24 months.] The criteria and classification of diabetes are presented in greater detail in the ISPAD Clinical Practice Consensus Guidelines: Definition, Epidemiology, Diagnosis and Classification of Diabetes (37) Diagnostic criteria for diabetes are based on BG measurements and the presence or absence of symptoms (E) (38,39). Three ways to diagnose diabetes are possible and each, in the absence of unequivocal hyperglycemia, must be confirmed, on a subsequent day, by any one of the three methods given below. Diabetes is diagnosed when: A fasting plasma glucose (FPG) is ≥ 7.0 mmol/l (126 mg/dl) or The post challenge plasma glucose is > 11.1 mmol/l (200 mg.dl) performed as described by the World Health Organization (39), using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. or Symptoms of diabetes and a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/L). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. Diabetes in children, including T2DM, usually presents with characteristic symptoms such as polyuria, polydipsia, blurring of vision, and weight loss, in association with glycosuria and, in some cases, ketonuria. In its most severe form, ketoacidosis or hyperglycemic hyperosmolar state may develop and lead to stupor, coma, and in absence of effective treatment, death. The diagnosis is usually confirmed quickly in symptomatic individuals by measurement of a marked elevation of the blood glucose level. In this situation, if ketones are present in the blood or urine, treatment is urgent. Waiting another day to confirm the hyperglycemia may be dangerous in allowing ketoacidosis or hyperosmolarity to evolve. In the absence of symptoms or presence of mild symptoms of diabetes, hyperglycemia detected incidentally or under conditions of acute infective, traumatic, circulatory, or other stress may be transitory and should not in itself be regarded as diagnostic of diabetes. The diagnosis of diabetes, in the absence of symptoms, should not be based on a single plasma glucose concentration. Diagnosis may require continued observation with fasting and/or 2-h postprandial BG levels and/or an oral glucose tolerance test (OGTT). An OGTT should not be performed if diabetes can be diagnosed using fasting, random, or postprandial criteria, as excessive hyperglycemia can result using a fasting OGTT in these circumstances. (E). If doubt remains, periodic re-testing should be undertaken until the diagnosis is established or refuted. There are individuals whose glucose levels do not meet the criteria for diabetes, but are too high to be considered normal. Impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) are intermediate stages in the natural history of disordered carbohydrate metabolism between normal glucose homeostasis and diabetes (E). IFG and IGT are not interchangeable and represent different abnormalities of glucose regulation. IFG is a measure of disturbed carbohydrate metabolism in the basal state, while IGT is a dynamic measure of carbohydrate intolerance after a standardized glucose load. Patients with IFG and/or IGT are now referred to as having 'pre-diabetes', indicating the relatively high risk for development of diabetes in these patients (38). IFG and IGT may be associated with the metabolic syndrome (MS), which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-high density lipoprotein type, and hypertension. Individuals who meet the criteria for IGT or IFG may be euglycemic in their daily lives as shown by normal or near-normal glycated hemoglobin levels, and those with IGT may manifest hyperglycemia only when challenged with an OGTT. FPG < 5.6 mmol/L (100 mg/dL)= normal fasting glucose. FPG 5.6–6.9 mmol/L (100–125 mg/dL)= IFG. FPG ≥ 7.0 mmol/L (126 mg/dL)= provisional diagnosis of diabetes (the diagnosis must be confirmed, as described above under 'Diagnostic criteria for type 2 diabetes'). The corresponding categories for IGT when the OGTT is used are as follows: 2-h postload glucose < 7.8 mmol/l (140 mg/dl)= normal glucose tolerance. 2-h postload glucose 7.8–11.1 mmol/l (140–199 mg/ dl)= IGT. 2-h postload glucose > 11.1 mmol/l (200 mg/dl)= provisional diagnosis of diabetes (the diagnosis must be confirmed with additional testing, as described above). After the diagnosis of diabetes is established, autoantibody testing should be considered when diagnosing and treating T2DM. Diabetes autoantibody testing should be considered in all pediatric patients with the clinical diagnosis of T2DM because of the high frequency of islet cell autoimmunity in otherwise "typical" T2DM. Antibodies will indicate an earlier need for insulin as well as the need to monitor for thyroid autoimmunity and to consider other autoimmune disorders associated with T1DM. (E) Diabetes autoantibody testing also should be considered in overweight/obese children > 13 years of age with a clinical picture of T1DM (weight loss, ketosis/ketoacidosis), some of whom may have T2DM (E) Insulin resistance is an impaired response to the physiologic effects of insulin, including effects on glucose, lipid, and protein metabolism, and on vascular endothelial function. Insulin resistance occurs in most tissues including liver, muscle, and fat tissue and is influenced by sex, age, race/ethnicity, stage of sexual maturation, and total adiposity. While visceral adiposity is important in insulin resistance in adults, the specific contribution of visceral adiposity to insulin resistance in the pediatric population remains uncertain. Several events in development may be associated with increased risk for the insulin resistance syndrome. These include premature adrenarche in girls (pubic hair appearing before the age of 8 years) and being born small for gestational age. Girls with a history of premature adrenarche are at increased risk for ovarian hyperandrogenism and PCOS and thus, insulin resistance (40). Children born small for gestational age are at increased risk for insulin resistance related to decreased intrauterine growth (41) and also at increased risk for premature adrenarche. Diabetes is only one manifestation of the insulin resistance syndrome or the MS (22, 42–50). Other associations include: Obesity: Obesity has deleterious associations with morbidity and cardiovascular risk independent of effects related to insulin resistance and diabetes (51–54). Nephropathy: Albuminuria (either micro- or macro- ) is present at the time of diagnosis in a substantial number of adolescents with T2DM and prevalence increases with duration of diabetes (24). Proteinuria and focal segmental glomerular sclerosis have also been reported in African-American adolescents with severe obesity, in the absence of diabetes (55). Hypertension; Hypertension is estimated to account for 35–75% of diabetes complications, both microvascular and macrovascular (56). Diabetes or impaired glucose tolerance doubles the risk of developing hypertension (57). In addition, there is a possible genetic predisposition to hypertension in T2DM related to the associated angiotensin converting enzyme genotype (58). Hypertension in T2DM is due to volume expansion and increased vascular resistance (59) related to reduced (NO)-mediated vasodilatation and increased activity of the renin-angiotensin system. Dyslipidemia: Hypertriglyceridemia and decreased high-density lipoprotein cholesterol are the hallmarks of T2DM dyslipidemia. Additional findings include elevated very low-density lipoprotein (VLDL), elevated LDL-c, elevated lipoprotein(a), and increased small dense LDL particles. Decreased lipoprotein lipase activity, increased lipoprotein glycation and increased lipoprotein oxidation render the lipoproteins more atherogenic. (60,61) Ovarian hyperandrogenism and premature adrenarche (62): PCOS is being increasingly recognized in adolescents as part of the insulin resistance syndrome. Adolescents with PCOS have ∼40% reduction in insulin-stimulated glucose disposal compared to body composition matched non-hyperandrogenic control subjects (59). Decreasing insulin resistance may improve ovarian function and increase fertility. NAFLD: Hepatic steatosis is present in 25–45% of adolescents with T2DM and more advanced forms of NAFLD, such as non-alcoholic steatohepatitis, are increasingly common and associated with progression to cirrhosis (24, 64). NAFLD now represents the most common cause of cirrhosis in children and the most common reason for liver transplantation in adults in the US. Systemic inflammation: elevated C-reactive protein, inflammatory cytokines and white blood cell counts in obese adolescents have been associated with increased risk for cardiovascular disease in adults (54). Additional health problems related to obesity include Obstructive sleep apnea (OSA) with associated pulmonary hypertension (65), orthopedic problems resulting in diminishing physical activity (66,67), pancreatitis, cholecystitis and pseudotumor cerebri. In adults, there is a strong association between level of hyperglycemia and increased risk of macrovascular disease. Hyperglycemia, dyslipidemia, and hypertension are contributors to the acceleration of atherosclerosis in T2DM, along with oxidative stress, glycation of vascular proteins, and abnormalities of platelet function and coagulation. Defective endothelium dependent vasodilatation is an additional factor accelerating atherosclerosis in T2DM. It is an early sign of increased risk for cardiovascular disease, and predictive of cardiovascular events (68) (B) and occurs in obese children relative to their level of obesity and degree of insulin resistance (69) (B). Co-morbidities characteristic of the insulin resistance syndrome are commonly seen at diagnosis or appear early in the course of T2DM and should be tested for sooner than in T1DM, where these disorders are complications of the diabetes rather than co-morbid conditions (70, 71) (B). A more complete discussion of testing for complications/co-morbidities is presented in the ISPAD Clinical Practice Guidelines for microvascular and macrovascular complications (72). Either micro- or macro-albuminuria, may be present at the time of diagnosis and albuminuria should be evaluated at diagnosis and annually thereafter (55, 72)(E). Likewise, hypertension may be present at, or prior to diagnosis of diabetes and each individual should be evaluated at every visit for hypertension. Dyslipidemia is more common in type 2 diabetes and in family members, (60,61) and should be screened for when metabolic stability is achieved. Evaluation for NAFLD should be done at diagnosis and annually thereafter (24)(E). Inquiries about puberty, menstrual irregularities and obstructive sleep apnea should be made at diagnosis and regularly thereafter (65)(E). Additional information is available in the ISPAD Clinical Practice Guidelines on complications. (72). Dyslipidemia, hypertension and albuminuria are more common in type 2 diabetes compared to type 1 diabetes and may be present at diagnosis and should be assessed after blood glucose control has been optimized. Confirmed hypertension (BP> 95% for age, gender and height) or albuminuria should be treated with an ACE inhibitor or, if not tolerated, an angiotensin receptor blocker (E). Combination therapy may be required if hypertension or albuminuria does not normalize on single agent treatment (E). Side effects are cough, hyperkalemia, headache and impotence (73). In addition, major congenital malformations have been reported with first trimester exposure to ACE inhibitors but not with other antihypertensive agents in non-diabetic women (74). Testing for dyslipidemia should be performed soon after diagnosis when BG control has been achieved and annually thereafter. (60,61) E Goal is LDL-C < 2.6 mmol (100 mg/dl) (68). If LDL-C is borderline (2.6-3.4 mmol;100–129 mg/ dl), or elevated (≥ 3.4 mmol; 130 mg/dl), repeat lipid profile should be performed in 6 months and dietary intervention to decrease total and saturated fat initiated. If LDL-C remains elevated after 3-6 months of attempting to optimize blood glucose control and diet, pharmacotherapy is warranted (72). Statin therapy has been shown to be safe and effective in children as in adults and should be the first pharmacologic intervention (72) although long term safety data are not available. Special attention should be paid to symptoms associated with muscles and connective tissues, as there is an increased risk of rhabdomyolysis The of T2DM in children and adolescents has required that with the of T1DM in children and adolescents the between the treatment of these T1DM is throughout the population to T2DM in North and Europe those with e.g. levels, less less well This has not been described for Asian T2DM. age. T1DM occurs throughout childhood, when is T2DM occurs in when family of families with a with T1DM have family with the disease, while 75% or more of families of the with T2DM have such The of these family to control weight and is with complications in the family and a of and in the treatment In most T1DM, beyond insulin and glucose is only for those individuals who are overweight and In all youth with T2DM, the is on and on glucose and effects of have the of T1DM and blood glucose insulin In in with an that dense increasingly and have to the of T2DM in children and its in of of including hypertension, dyslipidemia, and in the of complications may require more control in insulin T2DM than in T1DM, and attention to as by the Diabetes (21). also the ISPAD Clinical Practice Guidelines for diabetes and family for youth with type 2 diabetes is as important as it is in type 1 diabetes. and for T2DM will on and in insulin therapy and may not be required in T2DM will a greater on dietary and physical activity than is required for T1DM. should be given by with and of the and of youth with T2DM should be in a and age Because the of youth with T2DM are the ISPAD Guidelines for are to the of youth and families with T2DM The family will need to the of treatment of T2DM and to the of the required to T2DM should that the in the diagnosis type 1 type in a minority of patients can be and for the youth and The can be by the of blood glucose metabolism using therapy is to the metabolic of the specific of the of diabetes. is the of treatment of T2DM The family and should the of obesity and T2DM. must have an of the health and of the to an effective should be made in small and with the that these need to be The patient and family should be to monitor the and of and physical in any a and is for The and treatment for T2DM should include a and/or to a with and in of children with is should be to family and should be to all The family should be to dietary with including for weight reduced total and saturated fat increased and increased physical activity specific dietary are given in the ISPAD Guidelines for dietary should include: on and in of these and and for can result in substantial weight and is one of the most important for weight loss. and for the family and for the patient in an age including about dietary and activity related to and activity by of and using for that should be on in one with other activity as a family and should be in a or and not from a or of high density and in the the of and control of positive of or weight reduction in high and for and activity as for of and activity and for and should be for each patient and family that are to family and and should be to all A family or should be identified who is available to in physical activity with the may be to patients and family members. to with the dietary and is important to the of the should include: and an daily is to the of increased at reducing such as the and the time in related may be the most effective activity to be as a This should include daily to be more such as using of or to and to and and (E). for to and physical activity, including increases in daily (E). of blood glucose should be performed of should be and include a of fasting and postprandial glucose have been fasting a and daily post after the are while the within the (E). If the impaired glucose tolerance more frequent testing should be for of acute illness or when symptoms of or patients should more frequent testing and be in with their diabetes for (E). Patients on insulin or need to monitor for asymptomatic (E). should be at a year and if insulin is being used or metabolic control is should be continued in addition to pharmacologic therapy The of pharmacologic therapy is to decrease insulin resistance, increase insulin or to postprandial glucose The first used should be It has the over of reduction in without the risk of weight is decreased or remains and LDL-C and levels decrease during for type 2 diabetes in children and adolescents. of with over 3 months the need to a or insulin or in with a or a inhibitor Patients for should be on the effects of diabetes and oral agents on and oral agent should be used during pregnancy.

Background: Data regarding the prevalence of morbidity and mortality in patients of Type 2 Diabetes Mellitus (T2DM) is scanty in India. Objectives: To determine the prevalence of micro and macro vascular complications, acute metabolic complications, infections, Non Alcoholic Fatty Liver Disease (NAFLD) and cause of mortality in T2DM patients admitted to a tertiary care teaching hospital in Eastern India. Material and Methods: This was a hospital-based prospective study evaluating 150 T2DM patients admitted to a tertiary care institution in Eastern India. Diagnosis of micro and macro vascular complications, infections and NAFLD was made using standard protocols. In case of death, the most probable cause was noted. Results: Out of 150 patients, 14.7% of patients were newly diagnosed T2DM and out of them 41% of patients had vascular complications and 54.5% had infections. Of the total patients, 56% had nephropathy, 20% neuropathy, 17.3% retinopathy, 31.3% CVD, 11.3% CAD, 4.6% acute metabolic complications, 44% infections and 16.6% had NAFLD respectively. Macrovascular events occured earlier than microvascular complications. Multiple logistic regression analysis showed strong association of age, duration of diabetes, serum cholesterol, triglyceride, LDL-C with retinopathy (Regression coefficient β: -0.1086807, 0.4127152, -0.0513393, 0.0146429, 0.0587475; p < 0.05, < 0.001, < 0.05, < 0.05, < 0.05 respectively), while only duration of diabetes was strongly associated with nephropathy and neuropathy (Regression coefficient β: 0.2538751, 0.2261636; p < 0.001 for each). Increasing age was associated with CAD (Regression coefficient β: 0.055392; p < 0.05) and FBG was a risk factor for CVD (Regression coefficient β: 0.0055014; p < 0.05). 18.6% patients died due to diabetes related complications. Cardiovascular (CV)-related deaths (CVD+CAD) were most common cause (51.5%: CVD 36.4%, CAD 15.1%) to be followed by infections (27.3%) and then chronic kidney disease (12.1%). Conclusions: This study highlights the high prevalence of vascular complications and infections in T2DM patients of Eastern India. CV-related deaths were principal causes of death, similar to that in developed world.

Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan® , correlates with chronic vascular complications in a cohort of T2DM. We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan® and extensive evaluation of macrovascular and microvascular diabetic complications. Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication, 19% a macrovascular complication (prior myocardial infarction and/or ischaemic stroke) and 33% a microvascular one (26% chronic kidney disease [CKD]; 16% retinopathy; 6% neuropathy). In all, 171 (72%) patients had CAP≥248dB/m (ie hepatic steatosis), whereas 83 (21%) patients had LSM≥7.0/6.2kPa (M/XL probes) (significant liver fibrosis). CAP was not associated with any macro/microvascular complications, whereas LSM≥7.0/6.2kPa was independently associated with prior cardiovascular disease (adjusted OR 3.3, 95%CI 1.2-8.8; P=.02) and presence of microvascular complications (adjusted OR 4.2, 95%CI 1.5-11.4; P=.005), mainly CKD (adjusted OR 3.6, 95%CI 1.3-10.1; P=.01) and retinopathy (adjusted OR 3.7, CI 95% 1.2-11.9; P=.02). Neither diabetes duration nor haemoglobin A1c differed according to CAP or LSM values. Significant fibrosis, detected by FibroScan® , is independently associated with increased prevalence of macrovascular and microvascular complications, thus opening a new scenario in the use of this tool for a comprehensive evaluation of hepatic and vascular complications in patients with T2DM.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Background Vitamin D has a wide range of biological functions. The presence of vitamin D receptors (VDRs) in many tissues explains its diverse actions. The VDR gene is highly polymorphic, with many single nucleotide polymorphisms. The FokI polymorphism in the VDR gene is the only polymorphism that influences the size of the translated protein. Type 2 diabetes mellitus (T2DM) is a growing problem worldwide, it results from a complex of inheritance and environment interactions. Vitamin D deficiency and VDR gene polymorphism FokI have been linked to T2DM and diabetic microvascular and macrovascular complications.Aim The aim of this study is to determine the association of VDR gene polymorphism FokI with T2DM and diabetic microvascular and macrovascular complications in postmenopausal women.Participants and methods This study was carried out on 200 postmenopausal Egyptian women (50 healthy controls, 50 patients with T2DM without microvascular or macrovascular complications, 50 T2DM patients with microvascular complications, and 50 T2DM patients with macrovascular complications). VDR FokI genotypes were determined by PCR-restriction fragment length polymorphism analysis and hydroxy vitamin D (25OHD) levels were measured by enzyme linked immunosorbent assay.Results The prevalence of the polymorphic genotypes ff and the f allele was statistically significantly increased in diabetic patients than in controls (P<0.001), and the odds ratio was 7.84 (95% confidence interval: 1.75–35.09). There was a statistically significant increase in the polymorphic genotypes ff and the f allele in T2DM with microvascular or macrovascular complications compared with the control group (P=0.05). Plasma vitamin D (25OHD) levels were significantly lower in diabetic patients than in the control participants (P=0.032). On comparing the studied groups in terms of the plasma vitamin D (25OHD) levels, there was a statistically significant decrease in the levels in patients with microvascular and macrovascular complications in comparison with the control group (P<0.001).Conclusion The ff genotype and the f allele of VDR polymorphism FokI may represent a significant genetic molecular marker to predict the risk of diabetes and diabetic microvascular and macrovascular complications in postmenopausal women.

Increased oxidative stress in diabetes increases nitric oxide (NO) oxidation and low l-arginine (Arg) could further reduce NO and impair vascular function, thereby accelerating, in the long run, vascular complications. We therefore measured Arg and asymmetric dimethylarginine (ADMA) levels in patients with type 2 diabetes mellitus (T2DM) and healthy controls. Additionally, we observed the diabetic individuals over time to see if Arg and asymmetric dimethylarginine predicted T2DM complications. We examined baseline serum Arg and ADMA levels in a cohort of 105 participants with type 2 diabetes and compared them with an age- and weight-matched nondiabetic group of 137 individuals who served as a reference population. Additionally, we assessed whether Arg and/or ADMA predicted macrovascular and microvascular complications over 6years of follow-up. Serum Arg was lower in individuals with T2DM than in controls (64±28 vs 75±31μmol/L; P=.009) and inversely related to hemoglobin A1c (r=-0.2; P=.002). Over follow-up, we observed that participants with T2DM in the lowest quartile of Arg had increased risk for the subsequent evolution of nephropathy, peripheral neuropathy, and composite microvascular complications (odds ratio [OR]=5.5; 95% confidence interval [CI] -1.9 to 16; P=.002). The highest ADMA quartile was associated with increased risk for both microvascular (OR=4.5; 95% CI -1.4 to 14.1; P=.009) and 6.5-year incident macrovascular complications (OR=8.3; 95% CI 1.9-35.5; P=.004). l-Arginine levels are lower in individuals with T2DM than in matched controls. Both low Arg and high ADMA, independent of each other and adjusted for classical risk factors, predict the incidence of microvascular complications.

Bariatric Surgery Is Associated with a Reduction in Major Macrovascular and Microvascular Complications in Moderately to Severely Obese Patients with Type 2 Diabetes Mellitus

Diabetes mellitus is a non-communicable disease (NCD) with metabolic dysfunction that has attained epidemic proportions worldwide. Vascular complications account for the mortality and morbidity associated with diabetes. Hence, the study aimed to estimate the prevalence and risk factors for vascular complications in patients with type 2 diabetes mellitus (T2DM). A cross-sectional national multistage survey, the Saudi Health Interview Survey (SHIS), was used in this study, which surveyed individuals aged 15 years or older. After inclusion and exclusion criteria, 1240 diabetic patients' data were analyzed for sociodemographic data, risk factors, and prevalence of micro and macrovascular complications. Binary logistic regression with stepwise backward elimination was performed to build the optimal model to assess the determinants of macrovascular complications in diabetic patients. The strength of the associations was examined by estimating adjusted odds ratios (aOR) with their 95% CI. p-value < 0.05 was considered statistically significant. R Studio Version 1.2.1093 was used for statistical analysis RESULTS: Prevalence of micro and macrovascular complications in the diabetic patients was 6.05%, in which 3.5% had myocardial infarction, 1.2% had stroke and 1.9% had renal failure. The optimal model showed that for each year increase in age (aOR=1.05, 95%CI 1.02-1.07; p-value=0.000), smoking history (aOR=4.02, 95%CI 2.23-7.26; p-value=0.000), hypertensive patients (aOR=2.71, 95%CI 1.47-4.99; p-value=0.001), patients with low physical activity (aOR=4.32, 95%CI 1.26-14.82; p-value=0.001) were more likely to develop macro and microvascular complications in diabetic patients. The high prevalence of microvascular and macrovascular complications in diabetic patients poses a serious threat to public health in Saudi Arabia. A multisectoral approach needs to be undertaken to properly control and modify common risk factors at the community level.

IntroductionAdult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA.MethodsWe collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed.ResultsWe included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR–15) for T1DM and 42 years (IQR–15) for LADA (p = 0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p < 0.001). The mean BMI at diagnosis was 24.1 kg/m2 in T1DM group and 26.1 kg/m2 in LADA group (p = 0.042). In T1DM group, 67.4% of the patients had more than one positive autoantibody, comparing to 41.3% of LADA patients (p = 0.012). There was no statistical difference in what concerns to title of GAD autoantibodies, A1C and C-peptide at diagnosis of autoimmune aetiology. The presence of symptoms at diagnosis was associated with T1DM group (p < 0.001). The median daily insulin dose was 40 IU for T1DM (0.58 IU/kg) and 33.5 IU for LADA (0.57 IU/kg), with no statistical difference. LADA patients were more often under non-insulin antidiabetic drugs (p = 0.001). At 10 years follow up, 21.1% of T1DM patients and 63.3% of LADA patients had microvascular complications (p = 0.004). Diabetic nephropathy was present in 23.5% of T1DM patients and 53.3% of LADA patients (p = 0.047). At the last evaluation, 55.6% of T1DM and 82.6% of LADA patients had metabolic syndrome and this difference was independent of diabetes duration.ConclusionPatients with classic T1DM presented more often with symptoms, lower BMI and higher number of autoantibodies, which may be related to a more aggressive autoimmune process. Patients with LADA developed more frequently microvascular complications for the same disease duration, namely diabetic nephropathy, and had more often metabolic syndrome.