Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

Tailored nutritional interventions: A precision approach to managing gestational diabetes mellitus

Gestational diabetes mellitus(GDM)is a risk to maternal-fetal health due to uncertain diagnostic criteria and treatment options.Luo's study demonstrated the efficacy of customized nutritional therapies in controlling GDM.Tailored strategies led to significant body weight loss,improved glucolipid metabolism,and fewer prenatal and newborn problems.This holistic approach,which emphasizes the notion of’chrononutrition’,takes into account optimal meal timing that is in sync with circadian rhythms,as well as enhanced sleep hygiene.Implementing tailored dietary therapy,managing meal timing,and ensuring appropriate sleep may improve results for women with GDM,opening up a possible avenue for multi-center trials.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Type 2 Diabetes Mellitus in Children and Adolescents: Early Prevention and Non-Drug Therapy

The global rate of type 2 diabetes mellitus (T2DM) in youth has increased dramatically in the last 30 years. This increase mirrors the global epidemic of childhood obesity. Studies show that, compared to adults who develop T2DM, youth with T2DM ultimately suffer from more harmful symptoms. The prevalence of T2DM and obesity in youth signals a significant public health issue that financially burdens governments, families, and individuals. Since evidence suggests that T2DM in youth is different from both type 1 and type 2 diabetes in adults, researchers and clinicians face many difficulties in developing new treatments. Most treatment efforts have relied on drugs;however, recent studies suggest that non-drug therapy also effectively reduces obesity and diabetic symptoms. Healthier eating, increased physical exercise, and positive mental health, are often underappreciated factors towards managing obesity. Yet these lifestyle changes empower both young and older patients to independently fight diseases and attain better health. To manage the global health risk of obesity, further research addressing the prevention and nondrug early intervention of T2DM and obesity in youth is urgently needed. The present review focuses on the latest updates in the field.

γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus

BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.

Targeting epicardial adipose tissue:A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.

Autologous bone marrow derived stem cell therapy in patients with type 2 diabetes mellitus-defining adequate administration methods

AIM To carry out randomized trial for evaluating effects of autologous bone marrow derived stem cell therapy(ABMSCT) through different routes.METHODS Bone marrow aspirate was taken from the iliac crest of patients. Bone marrow mononuclear cells were separatedand purified using centrifugation. These cells were then infused in a total of 21 patients comprising three groups of 7 patients each. Cells were infused into the superior pancreaticoduodenal artery(Group Ⅰ), splenic artery(Group Ⅱ) and through the peripheral intravenous route(Group Ⅲ). Another group of 7 patients acted as controls and a sham procedure was carried out on them(Group Ⅳ). The cells were labelled with the PET tracer F18-FDG to see their homing and in vivo distribution. Data for clinical outcome was expressed as mean ± SE. All other data was expressed as mean ± SD. Baseline and post treatment data was compared at the end of six months, using paired t-test. Cases and controls data were analyzed using independent t-test. A probability(P) value of < 0.05 was regarded as statistically significant. Measures of clinical outcome were taken as the change or improvement in the following parameters:(1) C-peptide assay;(2) HOMA-IR and HOMA-B;(3) reduction in Insulin dose; subjects who showed reduction of insulin requirement of more than 50% from baseline requirement were regarded as responders; and(4) reduction in HbA 1c. RESULTS All the patients, after being advised for healthy lifestyle changes, were evaluated at periodical intervals and at the end of 6 mo. The changes in body weight, body mass index, waist circumference and percentage of body fat in all groups were not significantly different at the end of this period. The results of intra-group comparison before and after ABMSCT at the end of six months duration was as follows:(1) the area under C-peptide response curve was increased at the end of 6 mo however the difference remained statistically non-significant(P values for fasting C-peptide were 0.973, 0.103, 0.263 and 0.287 respectively and the P values for stimulated C-peptide were 0.989, 0.395, 0.325 and 0.408 respectively for groups Ⅰ?to Ⅳ);(2) the Insulin sensitivity indices of HOMA IR and HOMA B also did not show any significant differences(P values for HOMA IR were 0.368, 0.223, 0.918 and 0.895 respectively and P values for HOMA B were 0.183, 0.664, 0.206 and 0.618 respectively for groups Ⅰto Ⅳ);(3) Group Ⅰshowed a significant reduction in Insulin dose requirement(P < 0.01). Group Ⅱ patients also achieved a significant reduction in Insulin dosages(P = 0.01). The Group Ⅰand Group Ⅱ patients together constituted the targeted group wherein the feeding arteries to pancreas were used for infusing stem cells. Group Ⅲ, which was the intravenous group, showed a non-significant reduction in Insulin dose requirement(P = 0.137). Group Ⅳ patients which comprised the control arm also showed a significant reduction in Insulin dosages at the end of six months(P < 0.05); and(4) there was a non-significant change in the Hb A1 c levels at the end of 6 mo across all groups(P = 0.355, P = 0.351, P = 0.999 and P = 0.408 respectively for groups Ⅰto Ⅳ). CONCLUSION Targeted route showed a significant reduction in Insulin requirement at the end of six months of study period whereas the intravenous group failed to show reduction.

Effectiveness of cognitive behavior therapy for sleep disturbance and glycemic control in persons with type 2 diabetes mellitus:A community-based randomized controlled trial in China

BACKGROUND Poor sleep quality is a common clinical feature in patients with type 2 diabetes mellitus(T2DM),and often negatively related with glycemic control.Cognitive behavioral therapy(CBT)may improve sleep quality and reduce blood sugar levels in patients with T2DM.However,it is not entirely clear whether CBT delivered by general practitioners is effective for poor sleep quality in T2DM patients in community settings.AIM To test the effect of CBT delivered by general practitioners in improving sleep quality and reducing glycemic levels in patients with T2DM in community.METHODS A cluster randomized controlled trial was conducted from September 2018 to October 2019 in communities of China.Overall 1033 persons with T2DM and poor sleep quality received CBT plus usual care or usual care.Glycosylated hemoglobin A1c(HbAlc)and sleep quality[Pittsburgh Sleep Quality Index(PSQI)]were assessed.Repeated measures analysis of variance and generalized linear mixed effects models were used to estimate the intervention effects on hemoglobin A1c and sleep quality.RESULTS The CBT group had 0.64,0.50,and 0.9 lower PSQI scores than the control group at 2 mo,6 mo,and 12 mo,respectively.The CBT group showed 0.17 and 0.43 lower HbAlc values than the control group at 6 mo and 12 mo.The intervention on meanΔHbAlc values was significant at 12 mo(t=3.68,P<0.01)and that meanΔPSQI scores were closely related toΔHbAlc values(t=7.02,P<0.01).Intentionto-treat analysis for primary and secondary outcomes showed identical results with completed samples.No adverse events were reported.CONCLUSION CBT delivered by general practitioners,as an effective and practical method,could reduce glycemic levels and improve sleep quality for patients with T2DM in community.

Effects of anti-diabetic drugs on sarcopenia: Best treatment options for elderly patients with type 2 diabetes mellitus and sarcopenia

Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.

Manifestation of Diabetes Mellitus Type 1: A Questionnaire to Evaluate the Acceptance of Initial Intravenous Therapy

For families suddenly confronted with the diagnosis of a lifelong chronic disease, implementing a continuous iv. infusion represents restriction of movement and possibly also a psychological burden. We designed a questionnaire to evaluate the perception of pediatric patients and their parents for this treatment as part of a diabetes manifestation. Patients and their parents treated in the diabetes outpatient clinic at children’s university hospital in Mainz were asked for their opinion about “iv. infusion” and “frequency of blood taking” during their first stay in the hospital upon manifestation of diabetes. They assigned scores from 1 to 10 for the following parameters: “delivery of diagnosis”, “communication by doctor”, “execution of training”, “atmosphere during diabetes training”, “frequency of blood taking”, “iv. infusion” and “start of sc. insulin application”. Parents gave relatively high ratings. Parameters such as “frequency of blood taking” were rated with 6.1 on average. Ultimately, “frequency of blood taking”, “delivery of diagnosis” (6.11) and “iv. infusion of insulin” (6.5) scored lower than for instance “atmosphere of diabetes training” (7.95). Children awarded scores of 3.72 for “iv. infusion”, on average, whereas they scored 7.15 for the “doctor’s communication” and 7.28 for “diabetes training”. Asked if a decision in favor of a subcutaneous insulin injection right at the beginning of the therapy would have been preferable, parents were undecided. Therefore it cannot be concluded that an instant subcutaneous therapy has psychological advantages or disadvantages. The patients themselves (aged 12 - 17 years) were undecided, too, (58.3%) when asked for their preference of the subcutaneous insulin regime right at the beginning of the therapy. Nevertheless, the continuous infusion of insulin iv. was rated poorly by them. When planning further studies on this topic, the following questions should be analyzed: If the initial therapy had been started subcutaneously, would the manifestation be assessed differently by the family? Is the patients’ poor rating of the iv. insulin injection reproducible? Do other factors more greatly influence the decision for or against iv. insulin injection at the start of the therapy, such as the time needed for caretaking for the iv. injection by the nurses or possible side effects of an iv. injection? How can the start of the therapy be organized, when starting with sc. therapy, in particular regarding the first communication with patient and family?

“Diabegon”, a safe and effective polyherbal therapy for type 2 diabetes mellitus

AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, "Diabegon", in human subjects with type 2 diabetes mellitus.METHODS: A total of 33 human subjects with type 2 diabetes mellitus were recruited for the study and all anthropological and biochemical parameters were recorded at the time of registration. The subjects were given hot water extract obtained from 10 gm of "Diabegon" powder, "Diabegon kwath", on an empty stomach everyday in the morning under personal supervision for 6 mo. The therapeutic functions of the "Diabegon kwath" was assessed by monitoring the blood glucoselevels at monthly intervals and glycosylated hemoglobin, lipid profile and biomarkers of oxidative stress, liver and kidney function markers at three monthly intervals in the study subjects. RESULTS: Daily administration of hot water extract of "Diabegon" regularly for 6 mo resulted in significant reductions of blood glucose and glycosylated hemoglobin levels. There was also a significant increase in high density lipoprotein cholesterol levels with concomitant decreases in total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein. A significant improvement in glycosuria and proteinuria was also observed. Also, the subjects exhibited a significant improvement in enzymatic and nonenzymatic biochemical markers of oxidative stress. The kidney and liver functions remained normal and in fact improved in many subjects.CONCLUSION: The study which is first of its kind, advocates "Diabegon kwath" as a safe and effective Ayurvedic therapy for the treatment of human type 2 diabetes mellitus and further placebo controlled trial may substantiate the therapeutic efficacy of the formulation.

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Human pluripotent stem cell-derivedβcells:Truly immature isletβcells for type 1 diabetes therapy?

A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.

Gestational diabetes mellitus: Challenges for different ethnic groups

Ethnicity is defined as"belonging to a social groupthat has a common national or cultural tradition".Membership of certain ethnic groups has long been associated with increased risk of gestational diabetes mellitus(GDM).Studies that examined ethnic differences amongst women with GDM were often conducted in western countries where women from various ethnic backgrounds were represented.The prevalence of GDM appears to be particularly high among women from South Asia and South East Asia,compared to Caucasian,African-American and Hispanic communities.For some,but not all ethnic groups,the body mass index is a risk factor for the development of GDM.Even within a particular ethnic group,those who were born in their native countries have a different risk profile for GDM compared to those born in western countries.In terms of treatment,medical nutrition therapy(MNT)plays a key role in the management of GDM and the prescription of MNT should be culturally sensitive.Limited studies have shown that women who live in an English-speaking country but predominantly speak a language other than English,have lower rates of dietary understanding compared with their English speaking counterparts,and this may affect compliance to therapy.Insulin therapy also plays an important role and there appears to be variation as to the progression of women who progress to requiring insulin among different ethnicities.As for peri-natal outcomes,women from Pacific Islander countries have higher rates of macrosomia,while women from Chinese backgrounds had lower adverse pregnancy outcomes.From a maternal outcome point of view,pregnant women from Asia with GDM have a higher incidence of abnormal glucose tolerance test results post-partum and hence a higher risk of future development of type2 diabetes mellitus.On the other hand,women from Hispanic or African-American backgrounds with GDM are more likely to develop hypertension post-partum.This review highlights the fact that management needs to be individualised and the clinician should be mindful of the impact that differences in ethnicity may have on the clinical characteristics and pregnancy outcomes inwomen affected by GDM,particularly those living in Western countries.Understanding these differences is critical in the delivery of optimal antenatal care for women from diverse ethnic backgrounds.

Pharmacogenetic studies update in type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.

Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes mellitus

AIM: To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with type Ⅱ diabetes. METHODS: A total of 107 patients with type Ⅱ diabetes were randomly assigned into intensive and standard treatment groups. Patients in the intensive treatment group received preterax (perindopril/ indapamide) to control blood pressure, and gliclazide (diamicron) MR to control blood glucose. Patients in the standard treatment group received routine medications or placebo. Urinary microalbumin (UMA), urinary creatinine (UCR), the UMA/ UCR ratio, and visual acuity were monitored according to the study design of the ADVANCE trial. Direct ophthalmoscopy and seven-field stereoscopic retinal photography were used to examine the fundi at baseline,and repeated after 5 years of treatment. RESULTS: The characteristics of patients in both groups were well balanced at baseline. After 5 years of treatment, visual acuity was found to be decreased in the standard group (P=0.04), but remained stable in the intensive group. The severity of diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group (P=0.0006). The UMA/UCR ratio was not obviously changed in patients in the intensive group, whereas it was significantly increased in the standard group (P=0.00). CONCLUSION: Intensive control of blood glucose and blood pressure can decrease the incidence or slow the progression of microvascular complications in patients with type Ⅱ diabetes, and maintain stable vision.

Treatment of type 2 diabetes mellitus in the elderly

The prevalence of type 2 diabetes is expected to increase gradually with the prolongation of population aging and life expectancy. In addition to macrovascular and microvascular complications of elderly patients of diabetes mellitus, geriatric syndromes such as cognitive impairment, depression, urinary incontinence,falling and polypharmacy are also accompanied by aging. Individual functional status in the elderly shows heterogeneity so that in these patients, there are many unanswered questions about the management of diabetes treatment. The goals of diabetes treatment in elderly patients include hyperglycemia and risk factors, as in younger patients. comorbid diseases and functional limitations of individuals should be taken into consideration when setting treatment targets. Thus, treatment should be individualized. In the treatment of diabetes in vulnerable elderly patients, hypoglycemia, hypotension, and drug interactions due to multiple drug use should be avoided. Since it also affects the ability to self-care in these patients, management of other concurrent medical conditions is also important.

Critical review of bone health,fracture risk and management of bone fragility in diabetes mellitus

The risk of fracture is increased in both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,in contrast to the former,patients with T2DM usually possess higher bone mineral density.Thus,there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes.Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk.Moreover,some antidiabetic medications further enhance the fragility of the bone.On the other hand,antiosteoporosis medications can affect the glucose homeostasis in these patients.It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk.Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature.With the advancement in imaging technology,newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes.The purpose of this review is to explore the patho-physiology behind poor bone health in diabetic patients.Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism

Transient neonatal diabetes mellitus 1(TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1 /HYMAI. Whereas the function of HYMAI, a non-coding m RNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest(ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulinsecretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasgrf1 with roles in insulin secretion and β-cell proliferation. Collectively, concerted dysregulation of these target genes could contribute to the onset and course of TNDM1. Interestingly, Zac1 overexpression in β-cells spares the effects of stimulatory G-protein signaling on insulin secretion and raises the prospect for tailored treatments in relapsed TNDM1 patients. Overall, these results suggest that progress on the molecular and cellular foundations of monogenetic forms of diabetes can advance personalized therapy in addition to deepening the understanding of insulin and glucose metabolism in general.