We have studied major histocompatibility complex markers in Caucasian patients with typeIdiabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA- DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for typeIdiabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or […]
This cross sectional study was conducted at Lahore General hospital Lahore, Pakistan. All People aged between 12-20 years with Type-Idiabetes for at least one year attending the OPD were included in the study after obtaining inform consent. Ethical approval had been granted by the Institutional Review Board (IRB) of BIDE (Ref: BIDE/IRB-/Dr.MRiaz /03/09/15/0074). The trained interviewer approaches the parents (or legal guardian), for exclusion criteria, and invited families to enter a study of screening for psychological problems including depression and anxiety. Patients with known mental disorders or receiving psychotherapy were excluded. At the time of the study visit, informed consent was obtained. Information about participants demographic characteristics, co morbidities and complications, current treatment and medications were obtained by a trained diabetes educator. We considered participants to have co morbidities (kidney disease, celiac disease, hypertension, asthma, or polycystic ovarian syndrome) if they report having been diagnosed with any of these conditions. Participants or their parents/guardians were asked about the number of hospitalizations and Emergency visits and episodes of DKA and severe hypoglycemia that participants experienced in the previous 6 months. Sample size was estimated using the prevalence of depression among persons with Type-Idiabetes reported in previous study.  Using an estimated prevalence of 26%, 95% confidence intervals, and absolute precision of 1%, a sample size of 104 was determined.
The Long-Evans Tokushima Lean (LETL) rat, character- ized by rapid onset of insulin-dependent (typeI) diabetes mel- litus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic b cells, and no signif- icant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone sub- strain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to se- vere insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1 , on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Com- parative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes. ( J. Clin. Invest. 1997. 100:2015–2021.) Key words: insulin-dependent diabetes mellitus • insulitis • sus- ceptibility genes • linkage analysis • comparative mapping
Autoimmune Markers in Young Malaysian Patients with Type I Diabetes Mellitus ORIGINAL ARTICLE Autoimmune Markers in Young Malaysian Patients With Type 1 Diabetes Mellitus W M Wan Nazaimoont, K Nor Azm[.]
Total cholesterol and apo B100 concentrations are high- er in children with typeI DM (p<0.001) where triglyceri- des, apo AI, lp(a) and fibronectin concentrations are not statistically different (Tab. 1). Results of univariate regres- sion analysis in children with typeI DM, plasma FNp as the dependent variable are shown in Table 2. In the model that included age, BMI, gender, diabetes duration, HbA1c %, apo B100, apo AI, lp(a), cholesterol and trigly- cerides concentrations, only HbA1c and triglycerides were significant predictors of plasma FNp levels. Relations with gender and BMI did not reach significance level (p:0.08). Plasma levels of FNp decreased by 2.11±0.51 mg/dl for each unit increase in HbA1c % (p<0.001) and increased by 7.31±2.75 mg/dl for each increase in triglycerides mmol/L (p<0.01). This model explains 64.8 % of the varia- tion in plasma FNp concentration. Diabetic children with triglycerides concentration ≥1.13mmol/L had higher fibro- nectin levels compared to the diabetic and non-diabetic children with triglycerides <1.13mmol/L (p<0.01 and p<0.05) (Tab. 3).
Among the eight studies, only two used non-diabetes friends as a supportive group (2,3). It has been shown that non-diabetes friends increase emotional support in the suffering individual (3,16). Increasing knowledge among friends would conse- quently increase their understanding about their suffering friend, decreasing social stigma. Moreover, one of the concerns among diabetic children and adolescents was the fear of being rejected by their friends (17). In fact, they tend to be con- cerned about being rejected by the society and friends. On the other hand, they are more influenced by their friends and might be affected by behaviors that could be de- structive for their disease management. For instance, in a study on the effect of peers on choosing vague and risky options, re- searchers found that individuals tend to change their options in case of seeing dis- similar options selected by their peers and teammates. Researchers also found that this issue is also true for choosing risky and wrong behaviors. In other words, children and adolescents tended to opt for risky op- tions when they saw that most of their peers had also chosen the risky option (18). Con-
In our standard protocol, elevated blood glucose levels ( 9 300 mg/dl) observed at 12 days post-injection (dpi) are used to confirm diabetes in mice, while control mice exhibit blood glucose levels less than 200 mg/dl (not shown). In addition, we measured blood glucose levels at 4 and 19 dpi. Figure 2 demonstrates that at 19 dpi, both low and high STZ mice averaged blood glucose levels at or above 500 mg/dl, whereas control mice maintained normal non-fasting blood glucose levels less than 200 mg/dl. In contrast, at 4 dpi, only high-dose STZ mice exhibited significantly elevated blood glucose levels compared to controls. This suggests that the high-dose treatment induces a more rapid loss of insulin secretion (and therefore more rapid onset of diabetes) compared to low-dose treatment. Past studies indicate that the magnitude of STZ induction of serum glucose, urine volume, and glucosuria can, to some extent, correlate with dose concentration (25–27). Along these lines, the ef- fect of STZ on pancreatic beta cells has been shown to be dose- dependent by in vitro (28) and in vivo (26) studies. In the latter study, a greater number of pancreatic beta cells were shown to remain in mice after injection with multiple low doses of STZ (40 mg/kg for 5 days) compared to a single high-dose (200 mg/kg STZ) injection. Another indicator of the severity of diabetogenic and catabol- ic effects are changes in mouse body parameters (body, muscle, and fat pad mass), which were significantly decreased in both
Abstract: The burden of diabetes mellitus (DM) in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2) inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D) patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardio- vascular benefits associated with one of the SGLT2 inhibitors.
To the best of our knowledge, there has been published research on the effects of ethnicity in Malaysia and factors (quality of life, depression, and family problem) associated with diabetic control among young adults and adolescents with T1DM, but the factors that influence medication adherence were not covered in that study . The primary aim of this study was to evaluate adherence to insulin treatment and to identify factors that influence adherence behaviors in children with T1DM at Universiti Kebangsaan Malaysia Medical Center (UKMMC). In this study, the suitability of medication possession ratio (MPR) was evaluated by comparison with the gold standard of A1c, the predictor of glycemic control. In addition, demographic data of age, sex, and race, together with clinical data, for example, the presence of comorbidities and duration of time since diabetes diagnosis, were assessed to reveal predictors of adherence among patients with T1DM at UKMMC.
People with typeIdiabetes no longer produce insulin, and they must have insulin injections to use the glucose they obtain from eating. People with typeIdiabetes must give themselves insulin every day. Insulin can either be injected, which involves the use of a needle and syringe, or it can be given by an external or internal insulin pump, insulin pen, jet injector, or insulin patch. Extra amounts of insulin A may be taken before meals, depending on the blood glucose level and food to be eaten. Insulin cannot be taken as a pill. Because it is a protein, it would be broken down during digestion just like the protein in food. I must be injected into the fat under the skin for insulin to get into the blood. The amount of insulin needed depends on height, weight, age, food intake, and activity level. Insulin doses must be balanced with meal times and activities, and dosage levels can be affected by illness, stress, or unexpected events.
Diabetes is mainly divided into two types. In type-Idiabetes (T1DM), the b-cells of the islets of Langer- hans in the pancreas responsible for producing insulin are lost, typically from an attack from the immune system, causing an insulin deficiency in the body. In type-II diabetes (T2DM), cells become resistant to insulin signalling, failing to respond to it sufficiently. This is combined with either normal or increased insulin levels but can also develop into insulin deficiency through a relative loss of the insulin storage function of b-cells. Glucose levels in the body are important, as directly or indirectly they regulate many physiological processes, including glucose, glycogen metabolism. It also acts to control food intake (satiety) and maintaining long-term body weight but also regulates inflammation, vasodilatation and basic cell growth and replication. Thus, mishandling of glucose has wide-ranging consequences in the body. Among them is an alteration in the total plasma concentrations of micronutrients including some metal ions (Kaur and Henry 2014). This is thought to be caused by numerous factors, which include increased fluid loss from the body, an increased demand for micronutri- ents due to altered protein metabolism as well as defective metal transport due to oxidative stress (Kaur and Henry 2014; Maret 2017).
The reported prevalence of DPN varies with the type and the intensity with which it is sought. In the classic Diabetes Control & Complications Trial (DCCT) of diabetic complications in intensively rather than conventionally treated patients with typeIdiabetes mellitus,46 clinical neuropathy was defined as an abnormal clinical neurological examination plus either abnormal nerve conduction in at least two peripheral nerves or unequivocally abnormal autonomic-nerve testing. In patients without neuropathy at baseline, 9.8% of conventional and 3.1% of intensively treatment patients had developed it by 5 years. For patients in the secondary intervention cohort with retinopathy at baseline but not neuropathy, the rates were 16.1% for conventional and 7.0% for intensive treatment. Overall, when looking at a variety of studies (summarized by Shaw et al).(33), typeI diabetic prevalence figures vary from 13%–17% in hospitalized patients based on symptoms and signs, and 8%–54% with more comprehensive batteries in primary care or population-based screening. For type II diabetic patients, similar figures run from 19%–58% in hospital-based studies with some ancillary testing and 13%–46% in primary care or population-based screening more heavily weighted toward testing.
In this study, apelin ameliorated the blood glucose resulting in a significant reduction in serum glucose level in apelin treated obesity- induced diabetic group (type II DM) when compared with control subgroup, while it failed to induce the same effect in APL-INS vs. INS subgroups of STZ-induced diabetes (typeI DM) in the equal period of treatment. Furthermore, it also significantly decreases the serum insulin level in obesity induced diabetic group while, inducing insignificant changes on serum insulin in APL- INS vs. INS subgroups. In addition to above finding, apelin induced a significant reduction in HOMA-IR together with a significant rise in HOMA-β in rats of type II diabetes without any similar significant effect in rats of typeIdiabetes (APL-INS vs. INS). These data collectively support the hypothesis stats that apelin in conditions of obesity induced diabetes, has a peripheral unique insulin independent effect on glucose homeostasis, this effect may be increasing glucose uptake and improving insulin sensitivity status in insulin responsive tissues as adipose tissue and skeletal muscles resulting in improvement of beta cell function. This is not the case in typeIdiabetes models due to different pathophysiology of typeI DM, despite of some beneficial effects of apelin on beta cells as reducing endoplasmic reticulum stress , but there is no state of insulin resistant or adipokines dysregulation.
Aim: Bauhinia variegata Linn., syn: Kovidara and Kachnar, is a medium-sized deciduous tree generally found in sub-Himalayan region of India. Just about all parts of this plant are used in traditional medicine for the treatment of various ailments. A metabolic disorder, diabetes mellitus is one of the most common disorders. The current study was intended to appraise the efficacy of the ethanolic extract (EE) of B. variegata leaves in animal models of TypeI and Type II diabetes. Materials and Methods: TypeIdiabetes was induced by alloxan at the dose of 150 mg/kg (i.p.) in male albino Wistar rats while Type II diabetes was induced by high-fat diet and alloxan at the dose of 130 mg/kg (i.p.). Diabetic animals were treated with EE at the dose of 250, 500, and 1000 mg/kg. Glipizide (5 mg/kg) was used as standard treatment drug. Results: Treatment was given for 28 days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase (ALT), alkaline phosphatase (ALP), total proteins, albumin, creatinine, and blood urea nitrogen (BUN). In Type II diabetes, high-density lipoprotein levels in plasma and plasma insulin level were also evaluated. EE was also found to decrease cholesterol, triglyceride, creatinine, and BUN level in both types of diabetes. EE did not show any significant effect on plasma levels of aspirate aminotransferase, ALT, and ALP. EE was found to increase the albumin and total protein levels. Conclusion: Results obtained indicate that the EE of the leaves of B. variegata Linn. was able to lower the increased blood glucose levels in the selected animal models.
In the present study, we included a total of 200 subjects, out of which 50 had typeIdiabetes, 50 had type II diabetes, 50 had newly diagnosed diabetes, and 50 were subjects in the control group. For each individual participating in this study, post-prandial glucose concentration estimation in saliva and serum was done. All the subjects included in our study were informed about the study. An informed written consent was obtained from every subject included in the study.
Diabetes mellitus is a hyperglycemic, glucose metabolic syndrome that is caused by the destruction of Beta cells of pancreas that in general produced insulin which control blood glucose level. As typeIdiabetes mellitus T1DM is an auto immune disorder common in young ones and children’s in which body owns immune system is accountable for the demolition of pancreatic cells concerned with insulin secretion, in this disease auto reactive T cells destroy the beta islet of pancreas for which the main antigen was recognized as enzyme of the islet Glutamic acid decarboxylase (Medical microbiology & immunology 7 th edition). Diabetic influence nearly 346
one’s life but also for his or her other family members in terms of psychological distress and depression. The primary purpose is linked with quality of life but unfortunately there has been a lot of confusion regarding contextual quality of life. Now-a-days, a number of psychometric research tools have been developed for evaluation of QoL in relationship with social support and health locus of control. Diabetes is influential on major areas of QoL regardless of environment, culture and profession. However, it is postulated that the physical component must be coexisting with renal failure and diabetes, the psychological component is linked with typeIdiabetes emerged with depression and the social component is being effecting by destruction of family and friends. Therefore, it would be highly appreciated if different psychological tools and test could be translated into Urdu and being used at a wider level so that wider exploration of social support, health locus of control and quality of life in patients with typeI and type II diabetes may be addressed in future.
In this case-control study, 200 cases including 100 patients with typeIdiabetes and 100 patients with type II diabetes and also 100 non-diabetic individuals as a control group randomly were selected from patients having referred to Tabriz Central Laboratory in northwest Iran during July to September 2015. Inclusion criteria in diabetic groups were based on history (including family history and insulin therapy or received other drugs which reduce blood sugar), fasting blood sugar (more than 110 mg/dl) and HbA1c level (more than 6 percent). Control group were non-diabetic patients selected among those attending and matched with patient groups for age and gender. Patients with other metabolic disorders, immunocompromised and receiving immunosuppressive drugs were excluded from the present study.
replacement therapy (HRT) and oral contraceptives, respectively; and excluded patients with type 1 diabetes. Residual confounding by cigarette smoking has been suggested as a possible explanation for inconsistent associations between obesity and PVD (16). Excess risk for cardiovascular disease events associated with low BMI can also be associated with smoking- related diseases (such as chronic obstructive pulmonary disease (COPD) and lung cancer). Therefore, in sensitivity analyses we examined body size phenotypes with or without metabolic abnormalities and cardiovascular disease events only among individuals who reported never smoking cigarettes.
In view of their role in macrophage activation and induction of delayed-type hypersensitivity reactions, Th1 cells were re- garded as proinflammatory, while Th2 cells, which inhibit Th1 activity (see above), were considered anti-inflammatory (65, 84). Consistent with this characterization were the findings that IL-4 and IL-10—exclusive products of Th2 cells—inhibited IL-2-mediated responses and suppressed the production of the (proinflammatory) Th1 cytokines (20, 85). Accordingly, it was speculated that Th1 cytokines play a direct role in the patho- genesis and progression of IDDM, while Th2 cytokines should afford protection against Th1-mediated destruction of b islet cells. However, recent reports argued against this oversimpli- fication (61), as Th2 cells and their mediators were shown to be involved in IDDM pathogenesis through facilitation of pancre- atic mononuclear-cell infiltration (32, 87) and acceleration of b islet cell destruction (44, 68). This prompted the conclusion that IDDM is a Th1- and Th2-mediated disease (see below).