Displaying publications 521 - 540 of 565 in total

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  1. Borgquist S, Rosendahl AH, Czene K, Bhoo-Pathy N, Dorkhan M, Hall P, et al.
    Breast Cancer Res, 2018 08 09;20(1):93.
    PMID: 30092829 DOI: 10.1186/s13058-018-1026-7
    BACKGROUND: Long-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants.

    METHODS: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes.

    RESULTS: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively).

    CONCLUSIONS: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.

    Matched MeSH terms: Hypoglycemic Agents/adverse effects*
  2. Balasubramaniam S, Lim SL, Goh LH, Subramaniam S, Tangiisuran B
    Diabetes Metab Syndr, 2019 07 09;13(4):2585-2591.
    PMID: 31405680 DOI: 10.1016/j.dsx.2019.07.011
    BACKGROUND: Illness perceptions (IP) involve coping strategies and behavioural responses that can influence glycaemic control. Despite the importance of good glycaemic control, the majority of patients in Asia are not achieving glycaemic targets. An evaluation of IP in association with glycaemic control, medication adherence and chronic kidney disease (CKD) in Type 2 diabetes mellitus patients (T2DM) was carried out in an outpatient setting in Malaysia METHOD: A cross-sectional study was conducted using the Revised Illness Perception Questionnaire in a purposive sample of 384 T2DM patients.

    RESULTS: There were 55.7% females, median age was 58.2 years and median duration of diabetes was 13 years. The majority (79.4%) of patients had poor diabetes control (HbA1c ≥ 7.0%) and 39.6% of patients had low medication adherence. Patients with good glycaemic control had a higher Timeline Acute/Chronic and Emotional Representations score, hence they held the correct belief that diabetes is chronic and experienced negative emotions. Highly adherent patients had a higher Illness Coherence (χ2 = 21.385, p 

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use*
  3. Lim CTS, Nordin NZ, Fadhlina NZ, Anim MS, Kalaiselvam T, Haikal WZ, et al.
    BMC Nephrol, 2019 01 16;20(1):22.
    PMID: 30651084 DOI: 10.1186/s12882-019-1203-7
    BACKGROUND: Although there is a large volume of literature regarding the definition and epidemiology of. Type 2 diabetes nephropathy (T2DN). There has been a paucity of data focused on the rate of transition of T2 DN. Based on our personal observation a certain percentage of our incident end stage renal disease (ESRD) patients from T2DN experienced a rapid decline of renal function. Their rapid decline nature of glomerular filtration rate (GFR) of 46 to 60 mL/min per 1.73m2 per year have far exceeded the KDIGO definitions of acute kidney injury (abrupt decrease in kidney function occurring over 7 days or less), acute kidney disease (acute or subacute damage and/or loss of kidney function for a duration of between 7 and 90 days after exposure to an acute kidney injury initiating event (Chawla et al Nat Rev Nephrol 241-57 2017) or even rapid decliner (eGFR declines > 5 mL/min per 1.73m2 per year) (Chawla et al Nat Rev Nephrol 241-57 2017; Andrassy Kidney Int 622-623 2013).

    CASE PRESENTATION: We describe here three cases of type 2 diabetic patients that have rapid renal deterioration with rate of decline 46 - 60 mL/min per 1.73m2 per year. All the patients are heavily nephrotic. All of the renal biopsies done showed the classical diabetic changes, hypertensive changes, diffuse tubulointerstitial damage, and interstitial nephritis. All of the patients admitted to taking various form of traditional medications in hope of curing their renal disease.

    CONCLUSION: We wish to highlight that type 2 diabetics with massive nephrotic range proteinuria have enhanced risk of rapid renal function deterioration. The patients should be educated about the risks of rapid renal function deterioration when there is presence of heavy proteinuria. High grade proteinuria is likely to inflict the diffuse tubulointerstitial inflammation. The interstitial nephritis could be further worsened by traditional supplements consumption. Timely health education and advice must be undertaken to retard this unwanted rapid renal disease progression.

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  4. Mustaffa N, Ibrahim S, Abdullah WZ, Yusof Z
    Blood Coagul Fibrinolysis, 2011 Sep;22(6):512-20.
    PMID: 21537159 DOI: 10.1097/MBC.0b013e32834740ba
    Rosiglitazone is an oral hypoglycaemic agent of the thiazolidinedione group. This study aimed to assess changes in the diabetic prothrombotic state via plasminogen activity and changes in surrogate markers of atherosclerotic burden via ankle-brachial pressure index (ABPI) measurements after rosiglitazone was added to a pre-existing type 2 diabetes mellitus treatment regime. A nonblinded interventional study was designed. Fifty-nine patients were enrolled. Rosiglitazone-naïve patients were prescribed oral rosiglitazone 4 mg daily for 10 weeks. ABPI, plasminogen activity, glycosylated haemoglobin (HbA1c) and fasting lipid profile were measured pretreatment and post-treatment. Forty-eight patients completed the study. At the end of this study, mean plasminogen activity improvement was nearly 16% (P<0.05), mean ABPI improvement was 0.01 (P=0.439), mean HbA1c reduction was 0.51% (P<0.05), mean total cholesterol (TC) increase was 0.36 mmol/l (P<0.05), mean high-density lipoprotein cholesterol (HDL-C) increase was 0.15 mmol/l (P<0.05) and mean low-density lipoprotein cholesterol increased by 0.19 mmol/l (P=0.098). Rosiglitazone significantly improved plasminogen activity. There was also significant HbA1c reduction, and rise in both TC and HDL-C. Thus, rosiglitazone potentially improves the atherosclerotic burden and prothrombotic state. In future, more studies are needed to confirm the relationship between rosiglitazone, fibrinolytic system and atheromatous reduction in type 2 diabetes mellitus.
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage
  5. Rama Chandran S, A Vigersky R, Thomas A, Lim LL, Ratnasingam J, Tan A, et al.
    Diabetes Technol Ther, 2020 02;22(2):103-111.
    PMID: 31502876 DOI: 10.1089/dia.2019.0277
    Background:
    Complex changes of glycemia that occur in diabetes are not fully captured by any single measure. The Comprehensive Glucose Pentagon (CGP) measures multiple aspects of glycemia to generate the prognostic glycemic risk (PGR), which constitutes the relative risk of hypoglycemia combined with long-term complications. We compare the components of CGP and PGR across type 1 and type 2 diabetes.
    Methods:
    Participants: n = 60 type 1 and n = 100 type 2 who underwent continuous glucose monitoring (CGM). Mean glucose, coefficient of variation (%CV), intensity of hypoglycemia (INThypo), intensity of hyperglycemia (INThyper), time out-of-range (TOR <3.9 and >10 mmol/L), and PGR were calculated. PGR (median, interquartile ranges [IQR]) for diabetes types, and HbA1c classes were compared.
    Results:
    While HbA1c was lower in type 1 (type 1 vs. type 2: 8.0 ± 1.6 vs. 8.6 ± 1.7, P = 0.02), CGM-derived mean glucoses were similar across both groups (P > 0.05). TOR, %CV, INThypo, and INThyper were all higher in type 1 [type 1 vs. type 2: 665 (500, 863) vs. 535 (284, 823) min/day; 39% (33, 46) vs. 29% (24, 34); 905 (205, 2951) vs. 18 (0, 349) mg/dL × min2; 42,906 (23,482, 82,120) vs. 30,166 (10,276, 57,183) mg/dL × min2, respectively, all P 
    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  6. Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK
    Dig Dis Sci, 2020 02;65(2):623-631.
    PMID: 30684076 DOI: 10.1007/s10620-019-5477-1
    BACKGROUND AND AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.

    METHODS: In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial.

    RESULTS: There was a significant reduction in body mass index (median change, Δ = -0.7 kg per m2, p = 0.011), waist circumference (Δ = -3 cm, p = 0.033), systolic blood pressure (Δ = -9 mmHg, p = 0.024), diastolic blood pressure (Δ = -6 mmHg, p = 0.033), fasting blood glucose (Δ = -1.7 mmol/L, p = 0.008), total cholesterol (Δ = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Δ = -19 U/L, p = 0.013), volumetric liver fat fraction (Δ = -7.8%, p = 0.017), steatosis (Δ = -1, p = 0.014), ballooning (Δ = -1, p = 0.034), and fibrosis (Δ = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo.

    CONCLUSION: This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  7. Hasan SS, Kow CS, Bain A, Kavanagh S, Merchant HA, Hadi MA
    Expert Opin Pharmacother, 2021 Feb;22(2):229-240.
    PMID: 33054481 DOI: 10.1080/14656566.2020.1837114
    INTRODUCTION: Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19.

    AREAS COVERED: We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes.

    EXPERT OPINION: The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use*
  8. Nna VU, Abu Bakar AB, Ahmad A, Mohamed M
    Arch Physiol Biochem, 2021 Feb;127(1):51-60.
    PMID: 31072137 DOI: 10.1080/13813455.2019.1610778
    CONTEXT: Lactate is the preferred energy substrate for developing testicular germ cells. Diabetes is associated with impaired testicular lactate transport/utilisation, and poor sexual behaviour.

    OBJECTIVE: To examine the effects of metformin on parameters involved in testicular lactate production, transport/utilisation, and sexual behaviour in diabetic state.

    METHODS: Male Sprague-Dawley rats were assigned into normal control (NC), diabetic control (DC), and metformin-treated diabetic group (n = 6/group). Metformin (300 mg/kg b.w./day) was administrated orally for 4 weeks.

    RESULTS: Intra-testicular glucose and lactate levels, and lactate dehydrogenase (LDH) activity increased, while the mRNA transcript levels of genes responsible for testicular glucose and lactate transport/utilisation (glucose transporter 3, monocarboxylate transporter 4 (MCT4), MCT2, and LDH type C) decreased in DC group. Furthermore, penile nitric oxide increased, while cyclic guanosine monophosphate decreased, with impaired sexual behaviour in DC group. Treatment with metformin improved these parameters.

    CONCLUSIONS: Metformin increases testicular lactate transport/utilisation and improves sexual behaviour in diabetic state.

    Matched MeSH terms: Hypoglycemic Agents/pharmacology
  9. Burgeiro A, Fuhrmann A, Cherian S, Espinoza D, Jarak I, Carvalho RA, et al.
    Am J Physiol Endocrinol Metab, 2016 Apr 01;310(7):E550-64.
    PMID: 26814014 DOI: 10.1152/ajpendo.00384.2015
    Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology
  10. Gillani SW, Syed Sulaiman SA, Abdul MIM, Saad SY
    Curr Diabetes Rev, 2018;14(5):472-480.
    PMID: 28699483 DOI: 10.2174/1573399813666170710183736
    BACKGROUND: Disability is a key indicator implicating both overall morbidity and success of public health efforts to compress the period of morbidity among geriatrics for the overall population. Disabilities are more prevalent among diabetics than among those without diabetes.

    OBJECTIVE: This study aimed to determine self-monitoring practices, awareness to dietary modifications and barriers to medication adherence among physically disabled type 2 diabetes mellitus patients.

    METHODS: Interview sessions were conducted at diabetes clinic - Penang general hospital. The invited participants represented three major ethnic groups of Malaysia (Malay, Chinese & Indians). An openended approach was used to elicit answers from participants. Interview questions were related to participant's perception towards self-monitoring blood glucose practices, Awareness towards diet management, behaviour to diabetes medication and cues of action.

    RESULTS: A total of twenty-one diabetes patients between the ages 35 - 67 years with physical disability (P1-P21) were interviewed. The cohort of participants was dominated by Males (n=12) and also distribution pattern showed that majority of participants were Malay (n=10), followed by Chinese (n=7) and rest Indians (n=4). When the participants were asked in their opinion what was the preferred method of recording blood glucose tests, several participants from low socioeconomic status and either divorced or widowed denied to adapt telemontoring instead preferred to record manually. There were mixed responses about the barriers to control diet/calories. Even patients with high economic status, middle age 35-50 and diabetes history of 5-10 years were influenced towards alternative treatments.

    CONCLUSION: Study concluded that patients with physical disability required extensive care and effective strategies to control glucose metabolism.

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use*
  11. Chew BH, Lee PY, Cheong AT, Ismail M, Shariff-Ghazali S, Goh PP
    Prim Care Diabetes, 2016 10;10(5):383-6.
    PMID: 27459893 DOI: 10.1016/j.pcd.2016.07.003
    A persistent and increasing prevalence of diagnosed and undiagnosed diabetes mellitus has recently been reported in the National Health and Morbidity Survey 2015. This commentary recapitulates the relevant and valuable lessons in the Malaysian national diabetes registries to inform the healthcare stakeholders and policy makers on potential areas of clinical practice improvement and future researches. Under performance of the process measures and sub-optimal control of HbA1c, blood pressure and lipids profile were prevalent (<40% achieved treatment targets). Although these had improved slightly from 2009 to 2012, diabetes co-morbidities (hypertension and dyslipidaemia) and complications had also increased. Prevalence of insulin use had doubled, and lipid lowering agent use had increased about 50% in 2012 compared to 2009. We identified six clinical areas for urgent attention and improvement, and three potential areas for future research.
    Matched MeSH terms: Hypoglycemic Agents/therapeutic use*
  12. Islam MA, Alam F, Solayman M, Khalil MI, Kamal MA, Gan SH
    Oxid Med Cell Longev, 2016;2016:5137431.
    PMID: 27721914
    Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage
  13. Nna VU, Bakar ABA, Ahmad A, Mohamed M
    Andrology, 2019 01;7(1):110-123.
    PMID: 30515996 DOI: 10.1111/andr.12567
    BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.

    OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.

    MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.

    RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.

    DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.

    Matched MeSH terms: Hypoglycemic Agents/pharmacology*
  14. Hanipah ZN, Schauer PR
    Annu Rev Med, 2020 01 27;71:1-15.
    PMID: 31986081 DOI: 10.1146/annurev-med-053117-123246
    Metabolic surgery is increasingly becoming recognized as a more effective treatment for patients with type 2 diabetes (T2D) and obesity as compared to lifestyle modification and medical management alone. Both observational studies and clinical trials have shown metabolic surgery to result in sustained weight loss (20-30%), T2D remission rates ranging from 23% to 60%, and improvement in cardiovascular risk factors such as hypertension and dyslipidemia. Metabolic surgery is cost-effective and relatively safe, with perioperative risks and mortality comparable to low-risk procedures such as cholecystectomy, hysterectomy, and appendectomy. International diabetes and medical organizations have endorsed metabolic surgery as a standard treatment for T2D with obesity.
    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  15. Mosavat M, Omar SZ, Jamalpour S, Tan PC
    J Diabetes Res, 2020;2020:9072492.
    PMID: 32090124 DOI: 10.1155/2020/9072492
    Background: Defects in incretin have been shown to be related to the pathogenesis of type 2 diabetes. Whether such a deficiency happens in gestational diabetes mellitus (GDM) remains to be confirmed. We assessed the association of fasting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) with GDM. We also studied the longitudinal circulation of these peptides during pregnancy and afterwards.

    Methods: 53 women with GDM (30 managed with diet only (GDM-diet) and 23 treated with insulin (GDM-insulin)) and 43 pregnant women with normal glucose tolerance (NGDM) were studied, with GIP and GLP-1 levels measured at 24-28 weeks (E1), prior (E2) and after (E3) delivery, and postpuerperium (E4).

    Results: Basal GIP was shown to be low in GDM groups compared to NGDM in E1, and in E4 for GDM-diet. GLP-1 was low in GDM groups during pregnancy and afterwards. At E1, serum GIP and GLP-1 were inversely associated with GDM and participants with lower levels of GIP (<0.23 ng/mL) and GLP-1 (<0.38 ng/mL) had a 6 (95% CI 2.5-14.5)- and 7.6 (95% CI 3.0-19.1)-fold higher risk of developing GDM compared with the higher level, respectively. In the postpuerperium, when there is a drop in β-cell function, participants with previous GDM (pGDM) presented lower GLP-1 (in both GDM subgroups) and lower GIP in GDM-diet subgroup compared to controls.

    Conclusion: There is an independent, inverse association between fasting incretins and higher risk of GDM. Furthermore, lowered levels of these peptides may play an important role in the abnormality of glucose regulation following pregnancy.

    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  16. Candasamy M, Mohamed Elhassan SA, Kumar Bhattamisra S, Hua WY, Sern LM, Binti Busthamin NA, et al.
    Panminerva Med, 2020 Sep;62(3):155-163.
    PMID: 32208408 DOI: 10.23736/S0031-0808.20.03879-3
    Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) are two of the most commonly occurring diseases worldwide, especially among the elderly population. In particular, the increased prevalence of AD has imposed tremendous psychological and financial burdens on society. Growing evidence suggests both AD and T2D share many similar pathological traits. AD is characterized as a metabolic disorder whereby the glucose metabolism in the brain is impaired. This closely resembles the state of insulin resistance in T2D. Insulin resistance of the brain has been heavily implicated two prominent pathological features of AD, Aβ plaques and neurofibrillary tangles. Brain insulin resistance is known to elicit a positive feed-forward loop towards the formation of AD pathology in which they affect each other in a synergistic manner. Other physiological traits shared between the two diseases include inflammation, oxidative stress and autophagic dysfunction, which are also closely associated with brain insulin resistance. In this review and depending on these underlying pathways that link these two diseases, we have discussed the potential therapeutic implications of AD. By expanding our knowledge of the overlapping pathophysiology involved, we hope to provide scientific basis to the discovery of novel therapeutic strategies to improve the clinical outcomes of AD in terms of diagnosis and treatment.
    Matched MeSH terms: Hypoglycemic Agents/therapeutic use
  17. Subramanian R, Asmawi MZ, Sadikun A
    Acta Biochim. Pol., 2008;55(2):391-8.
    PMID: 18511986
    There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.
    Matched MeSH terms: Hypoglycemic Agents/pharmacology
  18. Pan CY, So WY, Khalid BA, Mohan V, Thai AC, Zimmet P, et al.
    Diabet Med, 2004 Sep;21(9):1007-13.
    PMID: 15317606 DOI: 10.1111/j.1464-5491.2004.01287.x
    AIM: To describe the clinical, biochemical and immunological characteristics of young-onset diabetes in Asia.
    METHODS: Clinical, biochemical and immunological variables were assessed in 919 newly diagnosed (duration less than 12 months) young onset Asian diabetic patients aged between 12 and 40 years. The subjects constituted 57% Chinese, 29% Indians and 14% Malays, recruited from diabetes centres in China, Hong Kong, India, Malaysia and Singapore.
    RESULTS: The mean age (+/- sd) was 31.6 +/- 7.2 years, with the majority (66%) in the 31-40 years age group. Mean body mass index (BMI) (+/- sd) was 25.3 +/- 5.0 kg/m2 with 47% exceeding the suggested Asian cut-off point for obesity (BMI > or = 25). Ethnic difference in clinical characteristics included BMI, blood pressure, mode of treatment and degree of insulin resistance. Most patients had a clinical presentation of Type 2 diabetes. About 10% had a classical combination of ketotic presentation, presence of autoimmune-markers and documented insulin deficiency indicative of Type 1 diabetes. Forty-eight percent were receiving oral hypoglycaemic agents (OHAs) while 31% were on diet only, 18% were receiving insulin and 2% were on a combination of insulin and OHA.
    CONCLUSION: Young onset diabetes patients in Asia represent a heterogeneous group in terms of their clinical and biochemical characteristics and classical Type 1 diabetes is relatively uncommon. The 5-year follow up study will determine the progress of these patients and help to clarify the natural history.
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage
  19. Liu S, Liu JJ, Gurung RL, Chan C, Yeo D, Ang K, et al.
    Ann Acad Med Singap, 2019 Jul;48(7):217-223.
    PMID: 31495867
    INTRODUCTION: The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.

    MATERIALS AND METHODS: A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.

    RESULTS: A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).

    CONCLUSION: Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.
    Matched MeSH terms: Hypoglycemic Agents/therapeutic use*
  20. Norlinah MI, Hamizah R, Md Isa SH, Wan Nazaimoon WM, Khalid BA
    Indian J Med Sci, 2009 Apr;63(4):131-8.
    PMID: 19414982
    BACKGROUND: The role of endothelial injury and circulating adhesion molecule in the development and progression of diabetic peripheral neuropathy in the long-term has been established previously.
    AIMS: To study the effects of short-term glycemic control using insulin and oral hypoglycemic agent therapy (OHA) on the peroneal nerve function and vascular cell adhesion molecule-1 (VCAM-1) and advanced glycation endproducts (AGE) levels in type 2 diabetic patients.
    SETTINGS AND DESIGN: A randomized controlled study involving poorly controlled (HbA1c, 7.5%-11%) type 2 diabetic patients attending the endocrinology outpatient center in a tertiary hospital in Kuala Lumpur.
    MATERIALS AND METHODS: Twenty-nine patients were randomized to receive insulin (n=15) or OHA (n=14) for 8 weeks. The glycemic variables (HbA1c, fasting plasma glucose [FPG], fructosamine), VCAM-1, serum AGE and the peroneal motor conduction velocity (PMCV) were measured at baseline and at 4-week intervals.
    STATISTICAL ANALYSIS USED: Paired 't' test or Kruskal Wallis test; and the unpaired 't' test or Mann-Whitney U test were used for within-group and between-group analyses, respectively. Correlation was analyzed using Spearman's correlation coefficient.
    RESULTS: Within-group analysis showed significant progressive improvement in HbA1c at weeks 4 and 8 in the insulin group. The PMCV improved significantly in both groups by week 8, and by week 4 (P = 0.01) in the insulin group. PMCV correlated negatively with VCAM-1 (P = 0.031) and AGE (P = 0.009) at week 8.
    CONCLUSION: Aggressive glycemic control with insulin improves the peroneal nerve function within 4 weeks. Improvement in the serum VCAM-1 and AGE levels correlated significantly with improvement in peroneal nerve conduction velocity only in the insulin group.
    Study site: Tertiary endocrinology outpatient center in Kuala Lumpur, Malaysia
    Matched MeSH terms: Hypoglycemic Agents/administration & dosage
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