Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

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.

Are proton pump inhibitors a new antidiabetic drug? A cross sectional study

AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any department during the fi rst semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was signif icantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to-0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies.

Advances in the Pathogenesis and Pharmacologic Treatment of Diabetic Cataracts

Diabetic cataract(DC)is a common complication prior to diabetes mellitus,which is a metabolic disease with pathogenesis including abnormal metabolism of polyphenol pathway(PP)and non-enzymatic glycosylation(NEG)of proteins,etc.The therapeutic drugs are mainly aldose reductase inhibitors(ARIs)and glycosylation inhibitors.The therapeutic regimens for DC are becoming more and more diversified due to the development of biological testing and clinical research technology,thus improving its clinical efficacy.With the development of biological testing and clinical research technology,the treatment options for DC have become increasingly diversified and the treatment specificity has been improved,improving its clinical efficacy.In order to comprehensively analyze the pathogenesis and pharmacological treatment of this disease,the following review is made.

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.

Drug Therapy Monitoring in Patients with Type 2 Diabetes and Hypertension

The aim of this paper is to detect, prevent and resolve DRP （drug-related problems） and NOM （negative outcomes associated with medication） in hospitalized patients with DM2 （type 2 diabetes） with HTN （hypertension） in a tertiary care clinic. Descriptive cross-sectional interventional study is used. DTM （drug therapy monitoring） was conducted in 73 patients using data obtained from clinical histories and interviews. NOM were detected based on symptoms and laboratory test results. The statistical significance was 0.05. It can be found that 23 DRP were detected, primarily in the category ＂likelihood of adverse effects＂ （30.43%） causing NOM in the ＂non-quantitative safety problem＂ category. The NOM detected were related to safety （62%）, effectiveness （24.5%） and necessity （13.5%）. Of the 68.57% of pharmacist interventions accepted, 48.57% were resolved and 20% were not resolved. A simple linear correlation （r = -0.34） analysis indicated a weak association between patient age and severity ofNOM. DTM made it＇possible to detect suspected DRP and NOM, which were then prevented or resolved, improving the control of HTN and DM2 and helping ensure better drug therapy outcomes for patients.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

Continuing episodes of pain in recurrent acute pancreatitis: Prospective follow up on a standardised protocol with drugs and pancreatic endotherapy

AIM To assess the outcomes of drug therapy(DT)followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.METHODS DT comprised of pancreatic enzymes and antioxidants failing which,endotherapy(ET;pancreatic sphincterotomy and stent placement)was done.The frequency of pain,its visual analogue score(VAS),quality of life(Qo L),serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET.Response was defined as at least 50%reduction in the severity of pain to below a score of 5.RESULTS Of the thirty nine patients analysed,21(53.9%)responded to DT and 18(46.1%)underwent ET.The VAS for pain(7.0±2.0 vs 1.3±2.5,P<0.001)and the number of days with pain per month decreased[1.0(1.0,2.0)vs 1.0(0.0,1.0),P<0.001],and the Qo L scores[55.0(44.0,66.0)vs 38.0(32.00,51.00),P<0.01]improved significantly during follow up.Similar significant improvements were seen in patients in the subgroups of DT and ET except for Qo L in ET.The serum C-peptide(P=0.001)and FE(P<0.001)levels improved significantly in the entire group and in the two subgroups of patients except for the C peptide levels in patients on DT.CONCLUSION A standardised protocol of DT,followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis,enhanced Qo L and improved pancreatic function.

Treatment of Incipient Diabetic Nephropathy by Clearing Away the Stomach-Heat,Purging the Heart Fire,Strengthening the Spleen and Tonifying the Kidney

It is the view of the authors that accumulation of heat and dampness in the heart and stomach and deficiency of both spleen and kidney with blood stasis would be the main predisposing factors in pathogenesis of incipient diabetic nephropathy. A controlled clinical study of 32 patients treatment with modified recipe of Wang Kentang’s Bai Fu Ling Wan, a proved formula of clearing away the stomach-heat, purging the heart fire, strengthening the stomach and tonifying the kidney, and simultaneously resolving blood stasis and turbid qi was performed. The total effective rate was 93.8%, superior to that in the control group treated with Capoton (59.9%). A marked improvement in symptoms, control of blood glucose level and reduction of urinary protein obtained in the treatment group suggests that this treatment is effective in retarding the development of the disease.

Twenty-eight Cases of Diabetic Foot Ulcer and Gangrene Treated with the Chinese Herbal Medicine Combined with Injection of Ahylsantinfarctase

Since 1995, the Chinese herbal medicine for supplementing qi and activating blood circulation combined with injection of ahylsantinfarctase into the femoral artery has been used in 28 cases of diabetes complicated with gangrene and ulcer of the foot, with quite good therapeutic effects as reported in the following.……

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Study of 82 Patients and Review of the Literatures

Background: Worldwide, diabetic nephropathy-DN is the leading cause of end-stage kidney disease-ESKD, DN is a common cause of renal failure with a reported frequency of 10% - 15% in type-2-diabetes-mellitus-T2DM patients, however there is a great discrepancy between countries. The aim of the pre-sent study is to evaluate the findings of kidney biopsies performed on diabetic patients. Materials and Methods: We studied native kidney histopathological findings in the period from January 2016 till end of December 2018 done for patients with T2DM with chronic kidney diseases-CKD. Results: A total of 82 DM-patients, 50 males (61%) and 32 females (39%) with age mean (95% CI) of 50.8 (47.1 - 55.2) years for all patients, ranged between 15 to 65 years. Histological findings showed that 57.3% of patients had DN. While focal-segmental-glomerulosclerosis-FSGS was present in 20.7%—primary in 8.6% and secondary in 12.1%. IgA represented 4.9%, while Lupus nephritis, Membranous and drug induced interstitial nephritis were each present in 3.7%. MCD was present in 2.4%. Lastly diffuse proliferative GN, ANCA associated glomerulonephritis, and hypertensive nephrosclerosis accounted for 1.2%. Conclusion: The prevalence of NDKD is remarkably frequent in DM patients who underwent kidney biopsy and FSGS was the most frequent diagnosis. To get a proper histopathological diagnosis, an adequate tissue biopsy is needed with an adequate number of glomeruli. There is a great need for more consideration to biopsy diabetic patients, as the finding of NDKD requires a different therapeutic approach. This, hopefully, will help to manage these patients better and therefore, ameliorate the progression to ESKD over time and therefore delay the need for RRT.

Treatment of Diabetic Neuropathy——Principles and Methods

Diabetic neuropathy (DN) is one of the common complications of diabetes mellitus (DM), its incidence can be as high as over 90%. The lesion can involve the sensory, motor and vegetative nerves. As a whole, the lesion can be divided into symmetric multiple neuropathy and asymmetric single neuropathy. Because the pathogenesis of the disease is not clear, no specific therapy is available so far. Besides control of blood sugar level, vitamin B, vasodilators and analgesics are often used in Western medicine for expectant treatment. Basic studies on chronic complications of DM show that aldose reductase and non-enzymatic glycosylation of protein are factors initiating the pathological changes, inhibitors against them have been tested in experimental studies and proved effective. Unfortunately, they are not used clinically due to severe side effects. Screening for herbal drugs to treat DN is still a popular trend in the TCM circle.

A Critical Review on Traditional Herbal Drugs: An Emerging Alternative Drug for Diabetes

Diabetes is a chronic metabolic disease reaching an epidemic proportion in many parts of the world. By the year 2025 it is expected that 333 million people of the world will have diabetes as their main ailment. As today, India assumes the position of the diabetic capital of the world with the highest percentage of its population suffering from diabetes. It is pathetic to mention that in proportion to its people suffering from diabetes, this country has very weak spending power for treatment because of wide spread poverty. Therefore, this review is aimed at opening up new vistas in realizing the therapeutic potential of Ayurveda in treatment of diabetes and other chronic diseases. All drugs which we have discussed in this review have a significant role in therapy of diabetes mellitus.

Diabetic Nephropathy and Management

Chronic kidney disease affects people worldwide. Approximately 1 out of 3 adults with diabetes have kidney disease. Among several etiological factors for CKD, diabetes mellitus (DM) and hypertension are the main factors. These factors not only cause CKD but are also responsible for several complications related to CKD. In this article, we have reviewed Diabetic Nephropathy (DN) in terms of etiology, pathophysiology, diagnosis, management, current guidelines for diabetic nephropathy management, and some of the research study findings. Diabetic nephropathy (DN) is the chief factor for end-stage renal disease (ESRD) development across the globe. The primary cause of DN is Diabetes Mellitus, which is an autoimmune lifestyle disorder having several etiological factors. Checking for urine albuminuria, estimated GFR (eGFR), and blood glucose are unswerving tests for DN diagnosis and subsequent monitoring. Controlling hyperglycemia, blood pressure, and proteinuria are critical in stopping the progression of DKD. Clinical practice and evidence-based medicine demonstrated that early diagnosis followed by treatment can prevent or halt DKD progression.

Research Progress of Treating Diabetic Nephropathy with Traditional Chinese Medicine

By collecting and sorting out the literature and journals on the clinical use of Chinese medicine in the treatment of diabetic nephropathy in recent years,it is concluded that Chinese medicine is effective in the treatment of DKD.Chinese medicine therapy has a unique role in the treatment of diabetic nephropathy.How to correct syndrome differentiation and treatment?Improving clinical effects is the research direction that all medical staff will work together in the future.

A CLINICAL TRIAL OF TANG SHEN NING FOR TREATMENT OF DIABETIC NEPHROPATHY

This paper reports the clinical trial of Tang Shen Ning ([symbol: see text], TSN) for treating diabetic nephropathy (incipient and clinical, as divided by Mogensen). The results showed that the total effective rate in treatment group (TSN + western medicine) was 90.0%, and that in the control group (simply with western medicine), 56.7%. TSN plays important roles in decreasing proteinuria and improving renal functions.

Type 2 diabetes mellitus affects eradication rate of Helicobacter pylori

AIM: To study the eradication rate of Helicobacter pylori (Hp) in a group of type 2 diabetes and compared it with an age and sex matched non-diabetic group.METHODS: 40 diabetic patients (21 females, 19 males;56±7 years) and 40 non-diabetic dyspeptic patients (20females, 20 males; 54±9 years) were evaluated. Diabetic patients with dyspeptic complaints were referred for upper gastrointestinal endoscopies; 2 corpus and 2 antral gastric biopsy specimens were performed on each patient. Patients with positive Hp results on histopathological examination comprised the study group. Non-diabetic dyspeptic patients seen at the Gastroenterology Outpatient Clinic and with the same biopsy and treatment protocol formed the control group.A triple therapy with amoxycillin (1 g b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg b.i.d.) was given to both groups for 10 days. Cure was defined as the absence of Hp infection assessed by corpus and antrum biopsies in control upper gastrointestinal endoscopies performed 6weeks after completing the antimicrobial therapy.RESULTS: The eradication rate was 50 % in the diabetic group versus 85 % in the non-diabetic control group (P＜0.001).CONCLUSION: Type 2 diabetic patients showed a significantly lower eradication rate than controls which may be due to changes in microvasculature of the stomach and to frequent antibiotic usage because of recurrent bacterial infections with the development of resistant strains.

The Present Situation of TCM Treatment for Diabetes and its Researches

Diabetes is a frequently encountered disease. There are now approximately 40 million diabetes patients in China1, most of them with diabetes II.

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.

Current cancer therapies and their influence on glucose control

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onset hyperglycemia,or of potentially severe clinical consequences when present.These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments,and the antimetabolite class of 5-fluorouracil-related drugs.Both of these classes have been in use in cancer therapy since the 1950s.Also considered are the phosphatidyl inositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth,proliferation and survival signaling pathways,and have been in clinical use as early as 2007.The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors(ICIs).These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors.For each drug class,the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use.The incidence of new glucose elevations in euglycemic individuals,as well as glycemic changes in those with established diabetes has been considered,as has the expected onset of hyperglycemia from their first use.This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels,whereas other classes can have lengthy delays of up to 1 year.A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs.There are distinct differences in the reversibility of glucose elevations after treatment is stopped,as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term.These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia,with clinical presentations ranging from potent yet transient insulin resistant states[type 2 diabetes mellitus(T2DM)-like]to rare permanent insulin-deficient causes of hyperglycemia.Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.