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Advances in the Generation of Functional β-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus

Kalra K, Chandrabose ST, Ramasamy TS, Kasim NHBA

Curr Drug Targets, 2018;19(13):1463-1477.
PMID: 29874998 DOI: 10.2174/1389450119666180605112917

Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.

Matched MeSH terms: Diabetes Mellitus/therapy*
Distal technology interventions in people with diabetes: an umbrella review of multiple health outcomes

Chakranon P, Lai YK, Tang YW, Choudhary P, Khunti K, Lee SWH

Diabet Med, 2020 12;37(12):1966-1976.
PMID: 31631398 DOI: 10.1111/dme.14156

AIM: To summarize and evaluate the existing evidence on the effectiveness of distal technology with regard to multiple health outcomes in people with diabetes.
METHODS: We searched PubMed, EMBASE and the Cochrane Database of Systematic Reviews from database inception to 31 August 2018 for systematic reviews and/or meta-analyses of studies that examined the impact of distal technology and reported any clinical or patient-related outcomes among people with type 1 or type 2 diabetes.
RESULTS: The umbrella review identified 95 reviews, including 162 meta-analyses with 46 unique outcomes. Evidence from meta-analyses of randomized controlled studies supports the use of distal technology, especially telehealth and mHealth (healthcare delivered by mobile technology), in people with diabetes for improving HbA1c values by 2-4 mmol/mol (0.2-0.4%). For other health outcomes, such as changes in fasting plasma glucose levels, risk of diabetic ketoacidosis or frequency of severe hypoglycaemia, the evidence was weaker. No evidence was reported for most patient-reported outcomes including quality of life, self-efficacy and medication-taking. The evidence base was poor, with most studies rated as low to very low quality.
CONCLUSION: Distal technologies were associated with a modest improvement in glycaemic control, but it was unclear if they improved major clinical outcomes or were cost-effective in people with diabetes. More robust research to improve wider outcomes in people with diabetes is needed before such technologies can be recommended as part of routine care for any patient group.

Matched MeSH terms: Diabetes Mellitus/therapy*
A comparison of knowledge of diabetes mellitus between patients with diabetes and healthy adults: a survey from north Malaysia

Yun LS, Hassan Y, Aziz NA, Awaisu A, Ghazali R

Patient Educ Couns, 2007 Dec;69(1-3):47-54.
PMID: 17720351 DOI: 10.1016/j.pec.2007.06.017

Objective: The primary objective of this study was to assess and compare the knowledge of diabetes mellitus possessed by patients with diabetes and healthy adult volunteers in Penang, Malaysia.
Method: A cross-sectional study was conducted from 20 February 2006 to 31 March 2006. We randomly selected 120 patients with diabetes mellitus from a diabetic clinic at the General Hospital Penang, Malaysia and 120 healthy adults at a shopping complex in Penang. Each participant was interviewed face-to-face by a pharmacist using a validated questionnaire, and they were required to answer a total of 30 questions concerning knowledge about diabetes mellitus using Yes, No or Unsure as the only response.
Results: The results showed that patients with diabetes mellitus were significantly more knowledgeable than the healthy volunteers about risk factors, symptoms, chronic complications, treatment and self-management, and monitoring parameters. Educational level was the best predictive factor for diabetes mellitus and public awareness.
Conclusion: Knowledge about diabetes mellitus should be improved among the general population.
Practice implications: This study has major implications for the design of an educational programme for diabetics and a health promotion programme as a primary prevention measure for the healthy population in general, and especially for those at high risk. The results could be useful in the design of future studies for evaluating patients' and the general public's knowledge about diabetes mellitus.

Matched MeSH terms: Diabetes Mellitus/therapy
Use of complementary and alternative medicine among patients with chronic diseases at outpatient clinics

Hasan SS, Ahmed SI, Bukhari NI, Loon WC

Complement Ther Clin Pract, 2009 Aug;15(3):152-7.
PMID: 19595416 DOI: 10.1016/j.ctcp.2009.02.003

OBJECTIVE: The primary objective of this study was to evaluate the use of complementary and alternative medicine among patients with chronic diseases at outpatient clinics. Another aim was to identify demographic and socio-economic factors that are associated with CAM use.
RESEARCH DESIGN AND METHODS: Face-to-face interviews of conveniently selected patients with chronic diseases were conducted in outpatient clinics of a general hospital. A validated data collection form was used to gather the information regarding pattern, perception, reasons, and perceived effect of CAM on the disease state. The other relevant information including demographics, diagnosis, indication, and treatment were collected from the patients' medical records.
RESULTS: Out of 321 patients interviewed in this study, 205 patients were using some form of CAM, and thus the utilisation rate was 63.9%. A significant number of patients (35.5%) were using CAM for diabetes mellitus. Thirteen types of CAM were identified in the study with the most common being vitamins supplements (48.2%), herbal medicines (26.4%), ginseng (4.7%) and traditional Chinese medicine (4.0%). The patients with higher education level, higher income, and aged more than 50 years were independently associated with CAM use. Majority of the patients (77.6%) reported that their condition had improved by using CAM.
CONCLUSION: The present study confirms the high frequency of CAM use among patients with chronic diseases in a Malaysian public hospital. The popularity of CAM indicated the patients' preference towards holistic approach to health care.
Study site: Outpatient clinics, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia

Matched MeSH terms: Diabetes Mellitus/therapy
Fulltext Three cases of permanent neonatal diabetes mellitus: genotypes and management outcome

Ooi HL, Wu LL

Singapore Med J, 2012 Jul;53(7):e142-4.
PMID: 22815030

Neonatal diabetes mellitus (DM) is defined as insulin-requiring DM in the first six months of life. Unlike type 1 DM, it is a monogenic disorder resulting from a de novo mutation in the genes involved in the development of the pancreas, β-cell mass or secretory function. The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel. Sulphonylurea, a KATP channel inhibitor, can restore insulin secretion, hence offering an attractive alternative to insulin therapy. We report three cases of neonatal DM and their genetic mutations. Two patients were successfully switched over to sulphonylurea monotherapy with resultant improvement in the quality of life and a more stable blood glucose profile. Patients with neonatal DM should undergo genetic evaluation. For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered.

Matched MeSH terms: Diabetes Mellitus/therapy*
Fulltext Cardiovascular risk factor treatment targets and renal complications in high risk vascular patients: a cohort study

Selvarajah S, van der Graaf Y, Visseren FL, Bots ML, SMART study group

BMC Cardiovasc Disord, 2011 Jul 05;11:40.
PMID: 21729268 DOI: 10.1186/1471-2261-11-40

BACKGROUND: To determine if recommended treatment targets, as specified in clinical practice guidelines for the management of cardiovascular disease, reduces the risk of renal complications in high risk patient populations.
METHODS: This was a cohort study. Participants in Utrecht, The Netherlands either at risk of, or had cardiovascular disease were recruited. Cardiovascular treatment targets were achievement of control in systolic and diastolic blood pressure, total and low-density cholesterol, and treatment of albuminuria. Outcome measures were time to development of end stage renal failure or symptomatic renal atherosclerotic disease requiring intervention.
RESULTS: The cohort consisted of 7,208 participants; 1,759 diabetics and 4,859 with clinically manifest vascular disease. The median age was 57 years and 67% were male. Overall, 29% of the cohort achieved the treatment target for systolic blood pressure, 39% for diastolic blood pressure, 28% for total cholesterol, 31% for LDL cholesterol and 78% for albuminuria. The incidence rate for end stage renal failure and renal atherosclerotic disease reduced linearly with each additional treatment target achieved (p value less than 0.001). Achievement of any two treatment targets reduced the risk of renal complications, hazard ratio 0.46 (95% CI 0.26-0.82). For patients with clinically manifest vascular disease and diabetes, the hazard ratios were 0.56 (95% CI 0.28 - 1.12) and 0.28 (95%CI 0.10 - 0.79) respectively.
CONCLUSION: Clinical guidelines for cardiovascular disease management do reduce risk of renal complications in high risk patients. Benefits are seen with attainment of any two treatment targets.

Matched MeSH terms: Diabetes Mellitus/therapy
Fulltext Glycaemic control of diabetic patients in an urban primary health care setting in Sarawak: the Tanah Puteh Health Centre experience

Wong JS, Rahimah N

Med J Malaysia, 2004 Aug;59(3):411-7.
PMID: 15727390 MyJurnal

Achieving glycaemic goals in diabetics has always been a problem, especially in a developing country with inadequate facilities such as in Sarawak in Malaysia. There are no reported studies on the control of diabetes mellitus in a diabetic clinic in the primary health care setting in Sarawak. This paper describes the profile of 1031 patients treated in Klinik Kesihatan Tanah Puteh Health Centre. The mean age was 59 years, the mean BMI 27 kg/m2. There was a female preponderance and mainly type-2 diabetes. Mean HbA1c was 7.4%. Glycaemic control was optimal in 28% (HbA1c <6.5%), fair in 34% (HbA1c 6.5-7.5%) and poor in 38% (HbA1c >7.5%). Reasonable glycaemic control can be achieved in the primary health care setting in Sarawak.
Study site: Klinik Kesihatan Tanah Puteh, Sarawak, Malaysia

Matched MeSH terms: Diabetes Mellitus/therapy*
Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

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: Diabetes Mellitus/therapy*
The Lancet Commission on diabetes: using data to transform diabetes care and patient lives

Chan JCN, Lim LL, Wareham NJ, Shaw JE, Orchard TJ, Zhang P, et al.

Lancet, 2021 Dec 19;396(10267):2019-2082.
PMID: 33189186 DOI: 10.1016/S0140-6736(20)32374-6
Matched MeSH terms: Diabetes Mellitus/therapy*
Fulltext A retrospective review of diabetic nephropathy patients during referral to the sub-urban nephrology clinic

Menon R, Mohd Noor FS, Draman CR, Seman MR, Ghani AS

Saudi J Kidney Dis Transpl, 2012 Sep;23(5):1109-14.
PMID: 22982937 DOI: 10.4103/1319-2442.100972

Diabetic nephropathy (DN) has become the most common cause of end-stage renal failure. Early referral and specific nephrology treatment could delay the disease progression and should reduce the treatment cost, mortality and morbidity rate in these patients. This is a single-center, retrospective review of all DN patients referred to the nephrology clinic in Hospital Sultan Ahmad Shah, Temerloh, from 2000 to 2009, to study and define the clinical characteristics of DN patients at the time of the referral to the nephrology clinic. A total of 75 patient case records were reviewed. Forty-three (57.3%) of them were males, with a median age of 64.3 ± 8.5 years at the time of referral. Only 14.7% of them had blood pressure lower than 125/75 mmHg. Co-morbid and disease-related complications were also commonly diagnosed and 28.4% (n = 21) had ischemic heart disease, 23% (n = 17) had diabetic retinopathy and 20.3% (n = 15) had diabetic neuropathy. The mean serum creatinine at the time of referral was 339.8 ± 2.3 μmol/L, gylcated hemoglobin A 1c (HbA1C) was 8.1 ± 2.0 %, serum fasting glucose was 9.6 ± 4.7 mmol/L, serum cholesterol was 5.4 ± 1.2 mmol/L and hemoglobin level was 10.6 ± 2.9 g/dL. Although female patients were less frequently seen in the early stages of chronic kidney disease (CKD), they comprised at least 72.7% of CKD stage 5 (male:female; 6:16, P <0.05). Twenty-nine percent (n=22) of them were referred at CKD stage 5, 48% (n=36) were at CKD stage 4, 17.3% (n=13) were at CKD stage 3, 4% (n=3) were at CKD stage 2 and 1.3% (n=1) was at CKD stage 1. Advanced CKD patients were frequently prescribed with more antihypertensives. CKD stage 5 patients were prescribed with two-and-half types of antihypertensive as compared to two types of anti-hypertensive in CKD stage 2 and stage 3. Furthermore, ACE-inhibitors (ACE-I) were less frequently prescribed to them. Only 22.7% (n=5) of CKD stage 5 patients received ACE-I and 30% (n=11) in CKD stage 4 patients as compared to 53.4% (n=7) in CKD patients stage 3. This review shows that DN patients were referred late to the nephrologists and the overall disease management was suboptimal. Antihypertensive requirement was also increased and ACEIs were less frequently prescribed in the advanced diabetic nephropathy patients.
Study site: Nephrology Clinic, Hospital Sultan Ahmad Shah, Temerloh, Pahang, Malaysia

Matched MeSH terms: Diabetes Mellitus/therapy*