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Fulltext Management of T1DM in children and adolescents in primary care

Hong Y, Hassan N, Cheah YK, Jalaludin MY, Kasim ZM

Malays Fam Physician, 2017;12(2):18-22.
PMID: 29423125

The Clinical Practice Guidelines on the Management of Type 1 Diabetes Mellitus in Children & Adolescents was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2015. A systematic review of 15 clinical questions was conducted using the evidence retrieved mainly from MEDLINE and Cochrane databases. Critical appraisal was done using the Critical Appraisal Skills. Recommendations were formulated on the accepted 136 evidences using the principles of Grading Recommendations, Assessment, Development and Evaluation tailored to the local setting. Type 1 diabetes mellitus is a chronic disease, which usually occurs at an early age, and is associated with various complications including retinopathy, nephropathy, neuropathy and cardiovascular morbidity. Good glycaemic control early in the disease results in lower frequency of chronic diabetes complications, which in turn reduces the healthcare cost. Accurate classification of diabetes and optimum management with the aim to achieve glycaemic targets is of utmost importance.

Matched MeSH terms: Diabetes Mellitus, Type 1
Blue deficiency in patients with diabetes mellitus without retinopathy - its clinical implications

Kaur S

Sains Malaysiana, 1996;25(2):41-49.

This study was conducted for 3 main purposes: 1) to determine if there was blue colour deficiency amongst diabetes mellitus (IDDM and NIDDM) patients without retinopathy, 2) to determine if the Dl5 test could be used to detect any colour vision defects amongst diabetics without retinopathy (all previous workers have used FM 100-Hue), and 3) to assess the performance of diabetics without retinopathy in detecting correct colour changes with the urine strip test. Thirty eight non-insulin dependent diabetes mellitus (NIDDM) and 30 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy participated in this study. A control group of 23 normal subjects were also included in the study. Dl5 colour vision test was performed under daylight conditions. Colour dependent urine glucose test (Glukotest) was also performed on all subjects. The study showed that 47.1% of diabetics (47.4% NIDDM and 46.7% IDDM patients) without retinopathy had a blue colour deficiency. Amongst the diabetics with a blue colour deficiency, 25% of diabetics (22% of NIDDM and 28.6% of IDDM patients) failed to accurately match the strip colour with the comparison chart on the bottle.
Kajian ini dilakukan untuk 3 tujuan: I) untuk menentukan samada terdapat gangguan penglihatan warna biru dalam pesakit diabetes mellitus (IDDM dan NIDDM) tanpa retinopati, 2) untuk menentukan samada ujian penglihatan warna Dl5 boleh digunakan untuk mengesan defek penglihatan warna dalam pesakit diabetes tanpa retinopati (kesemua kajian terdahulu menggunakan ujian FM 100-Hue). dan 3) untuk menilaikan prestasi pesakit diabetik tanpa retinopati dalam mengesan perubahan warna yang betul dengan menggunakan ujian strip urin. Tiga puluh lapan pesakit dengan non-insulin dependent diabetes (NIDDM) dan 30 pesakit dengan insulin dependent diabetes (IDDM) tanpa retinopati menyertai kajian ini. Kumpulan kawalan mengandungi 23 orang subjek yang normal juga terlibat di dalam kajian ini. Ujian penglihatan warna Dl5 dilakukan di bawah cahaya daylight. Ujian glukos urin berasaskan warna (Glukotest) dilakukan ke atas semua subjek. Kajian menunjukkan 47.1% pesakit diabetes (47.4% pesakit NIDDM dan 46.7% pesakit IDDM) tanpa retinopati mengalami defisiensi warna biru. Dalam kumpulan diabetik dengan defisiensi warna biru, 25% pesakit diabetes (22.2% adalah pesakit NIDDM dan 28.6% adalah pesakit IDDM) gagal untuk memadankan dengan tepat warna strip dengan carta perbandingan warna di atas botol.

Matched MeSH terms: Diabetes Mellitus, Type 1
Fulltext Accuracy, User Acceptability, and Safety Evaluation for the FreeStyle Libre Flash Glucose Monitoring System When Used by Pregnant Women with Diabetes

Scott EM, Bilous RW, Kautzky-Willer A

Diabetes Technol Ther, 2018 03;20(3):180-188.
PMID: 29470094 DOI: 10.1089/dia.2017.0386

BACKGROUND: Accuracy of the FreeStyle Libre™ Flash Glucose Monitoring System has not been evaluated in pregnant women with diabetes. The aim of this study was to determine accuracy (compared to self-monitoring of blood glucose [SMBG]), clinical safety, and acceptability of the FreeStyle Libre System when used at home by this population.
MATERIALS AND METHODS: Seventy-four participants, with type 1 (T1D, n = 24), type 2 (T2D, n = 11), or gestational (n = 39) diabetes, were enrolled across 13 sites (9 in United Kingdom, 4 in Austria). Average gestation was 26.6 ± 6.8 weeks (mean ± standard deviation), age was 30.5 ± 5.1 years, diabetes duration was 13.1 ± 7.3 years for T1D and 3.2 ± 2.5 years for T2D, and 49/74 (66.2%) used insulin to manage their diabetes. Sensors were worn for up to 14 days. Sensor glucose values (masked) were compared with capillary SMBG values (made at least 4 times/day).
RESULTS: Clinical accuracy of sensor results versus SMBG results was demonstrated, with 88.1% and 99.8% of results within Zone A and Zones A and B of the Consensus Error Grid, respectively. Overall mean absolute relative difference was 11.8%. Sensor accuracy was unaffected by the type of diabetes, the stage of pregnancy, whether insulin was used, age or body mass index. User questionnaires indicated high levels of satisfaction with sensor wear, system use, and comparison to SMBG. There were no unanticipated device-related adverse events.
CONCLUSIONS: Good agreement was demonstrated between the FreeStyle Libre System and SMBG. Accuracy of the system was unaffected by patient characteristics, indicating that the system is safe and accurate to use by pregnant women with diabetes.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood*; Diabetes Mellitus, Type 1/drug therapy
Fulltext An enzyme immunoassay for advanced glycosylation end-products in serum

Wan Nazaimoon WM, Khaid BAK

Malays J Pathol, 1998 Dec;20(2):83-9.
PMID: 10879267

We successfully developed an in-house, competitive enzyme immunoassay to measure advanced glycosylation end-products (AGE) in serum. The assay involved coating microtitre wells with AGE-BSA at 8 micrograms/ml for 4 hours, followed by overnight incubation of 20 microliters sample (prediluted at 1:6) with 80 microliters antiserum (1:8000). HRP-labelled goat anti-rabbit was used as the second antibody and 3,5',5,5'-tetramethylbenzidine dihydrochloride as the substrate. Incubation was carried out at 4 degrees C. As suggested in an earlier study, we standardised the AGE units against normal human serum (NHS). Thus, one AGE unit was defined as the inhibition that resulted when the 1:6 diluted NHS was assayed. Mean (+/- SD) AGE level in normal subjects (n = 37) was significantly lower than in diabetes subjects with microalbuminuria (n = 57) (6.0 +/- 0.7 versus 10.2 +/- 4.7 units/ml, p = 0.0001). With the availability of in-house assay and by standardising the AGE unit with the other laboratories, more studies could be undertaken and results compared, and possibly, further elucidate the roles of AGE in the pathogenesis of diabetic complications.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood; Diabetes Mellitus, Type 1/urine
Fulltext Microalbuminuria measurements by two in-house ELISA methods

Ng LC, Teng LC, Ng ML, Sazali BS, Khalid BA

Malays J Pathol, 2000 Dec;22(2):73-8.
PMID: 16329538

Detection of microalbuminuria is important in the management of diabetic patients since it is predictive of development of proteinuria and nephropathy. Two sensitive and specific in-house ELISAs for microalbuminuria were established and validated. One of the ELISAs was based on antigen coating while the other employed antibody coating. Recovery and linearity experiments gave acceptable results of 100 +/- 10%, while precision results were <10% for intra-assay and <12% for inter-assay coefficients of variation (CVs). The standard curve ranged from 10-625 ug/l, equivalent to 0.2-12.5 mg/l for urine samples diluted 1:20 fold. When the antibody coated ELISA was compared to antigen coated ELISA, a correlation of r=0.996 was obtained. When compared to commercial kits, the in-house ELISAs gave good correlations of r=0.961 versus the Boehringer Mannheim Micral Test strips and r=0.940 versus Ames Microalb Turbidimetry. The normal microalbumin reference ranges determined for 12h, first morning and random urine samples were 0.7-5.3 mg, 0.1-10.2 mg/l and 0.8-26.1 mg/l respectively. The normal albumin excretion rate (AER) was 1.0-7.3 ug/min while untimed urine samples gave results of 0.1-0.9 and 0.2-1.6 mg/mmol after dividing by creatinine concentrations. The ELISAs were used to detect microalbuminuria in 338 random urine samples from diabetic patients. A high percentage 47.9% was found to be positive for microalbuminuria and 18.0% had macroalbuminuria >25 mg/mmol. Thus screening for microalbuminuria together with creatinine measurements using random urine samples can be used for management of diabetic patients.

Matched MeSH terms: Diabetes Mellitus, Type 1/physiopathology; Diabetes Mellitus, Type 1/urine*
Type of diabetes and waist-hip ratio are important determinants of serum lipoprotein (a) levels in diabetic patients

Nawawi HM, Muhajir M, Kian YC, Mohamud WN, Yusoff K, Khalid BA

Diabetes Res Clin Pract, 2002 Jun;56(3):221-7.
PMID: 11947970 DOI: 10.1016/s0168-8227(02)00009-8

This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood*; Diabetes Mellitus, Type 1/physiopathology
Systolic hypertension and duration of diabetes mellitus are important determinants of retinopathy and microalbuminuria in young diabetics

Wan Nazaimoon WM, Letchuman R, Noraini N, Ropilah AR, Zainal M, Ismail IS, et al.

Diabetes Res Clin Pract, 1999 Dec;46(3):213-21.
PMID: 10624787 DOI: 10.1016/s0168-8227(99)00095-9

This cross-sectional study looked at the prevalence of microalbuminuria and retinopathy in a cohort of 926 young, Type 1 and Type 2 diabetes mellitus (DM) patients, and determined the factors which were associated with these microvascular complications. The prevalence of microalbuminuria, defined as the albumin:creatinine ratio > or = 2.5 (for males) or > or = 3.5 mg/mmol (for females), was 13.4% in Type 1 DM, 69.5% in insulin-requiring Type 2 DM and 16% in Type 2 DM treated only with oral hypoglycemic agents. Compared to those with normal renal functions, these patients were older (P < or = 0.01), had significantly elevated blood pressures (P < 0.01 or P = 0.0001), and in the case of Type 1 DM, with a higher body mass index (P = 0.0001) and waist-hip ratio (P < 0.01). The prevalence of diabetic retinopathy in Type 1 DM was found to increase with the duration of diabetes, from 1.4% in the newly-onset (< 5 years), to 9.9% in those with 5-10 years disease, to 35% among patients with more than 10 years of diabetes (P < 0.0001). In this study, it was also observed that 10% of the Type 2 DM patients already had retinopathy within 5 years of diagnosis, and the prevalence increased significantly to 42.9% (P < 0.0001) among patients who had been diabetics for more than 10 years. Stepwise multiple regression analysis showed that besides the disease duration, systolic blood pressure was the most common and significant determinant for both microalbuminuria and retinopathy in both types of DM, thus implying that in order to reduce the risk of microvascular complications in diabetes mellitus, systolic and not just the diastolic blood pressure, should be effectively controlled.

Matched MeSH terms: Diabetes Mellitus, Type 1/complications; Diabetes Mellitus, Type 1/urine
Fulltext Body composition in the pathogenesis and management of diabetes: a Malaysian perspective

Osman A, Khalid BA

Asia Pac J Clin Nutr, 1994 Mar;3(1):33-9.
PMID: 24351204

There is an increasing prevalence of diabetes mellitus around the world associated with rapid sociocultural development and changing lifestyles. Increased prevalence of obesity, with a higher consumption of animal products and lower consumption of fruits and vegetables, increases the risk of diabetes mellitus and other chronic degenerative diseases. Insulin-dependent diabetes (IDD) is caused by insulin deficiency, whereas the main feature of non-insulin-dependent diabetes (NIDD) which accounts for more than 90% of diabetics, is hyperinsulinemia and insulin resistance, which may eventually lead to actual insulin deficiency. Hyperinsulinemia is undesirable because it increases the risk of developing vascular disease. In Malaysia, the prevalence of NIDD in some communities now exceeds 5%, and of impaired glucose tolerance 10%. Along with these increases in prevalence of hyperglycemia are increases in prevalence of overweight (BMI>25) and almost certainly abdominal fatness. In terms of management, nutrition is given priority. Insulin and hypoglycemic drugs (sulphonylureas or biguanides), where required, may adversely affect body composition if overused. Newer therapeutic strategies require greater attention to the underlying problem in NIDD of abdominal fatness by attention to the relevant nutritional factors, physical activity and other lifestyle factors like cigarette smoking and alcohol. The greater impact of obesity and diabetes on Malaysian women as opposed to men also needs to be addressed.

Matched MeSH terms: Diabetes Mellitus, Type 1
Fasting growth hormone levels in diabetes mellitus

Nazaimoon WM, Ng ML, Khalid BA

Ann Acad Med Singap, 1993 Nov;22(6):861-3.
PMID: 8129344

Fasting serum growth hormone (GH) levels of different groups of diabetic patients were measured and compared to age-matched normal subjects. Insulin-dependent diabetes mellitus (IDDM) children (aged 12-17 years) were found to have significantly lower fasting GH levels than age-matched normal children (p < 0.001). In the adult age groups of 18-44 and 45-76 years, the IDDM patients showed increased fasting GH levels compared to age-matched normal subjects (p < 0.06 and p < 0.001 respectively) and non-insulin-dependent diabetes mellitus (NIDDM) patients (p < 0.05 and p < 0.001 respectively). The fasting GH levels of IDDM patients of the age group 18-44 years also showed significant correlations with glycated haemoglobin (r = 0.510, p = 0.002) and fasting blood sugar levels (r = 0.571, p = 0.01).

Matched MeSH terms: Diabetes Mellitus, Type 1/blood
Fulltext Evaluation of suppression of growth hormone levels following a 75g oral glucose tolerance test

Nazaimoon WM, Ng ML, Satgunasingam N, Khalid BA

Med J Malaysia, 1992 Jun;47(2):103-9.
PMID: 1494329

Growth hormone (GH) levels were measured after a 75g oral glucose load (OGTT) in normal adults, patients with impaired glucose tolerance (IGT), insulin-dependent diabetes mellitus (IDDM) and acromegaly. Nadir GH levels at 2-hour post-OGTT in normal subjects ranged from 0.4 to 8.4 mIU/L, the 95% confidence interval being 0.4-4.4 mIU/L. In IGT and IDDM subjects basal fasting GH levels were not significantly different from normal and did not alter during OGTT. The high fasting GH level measured in one each of the IGT and IDDM patients was suppressible at 1-hour after glucose intake. In contrast, acromegalic patients had elevated fasting GH levels (11.8-178 mIU/L) although in 3 patients, the levels were mildly elevated and overlapped with normal. OGTT failed or only partially suppressed GH secretion in all acromegalics. Therefore, elevated fasting GH levels are not diagnostic and OGTT is required for accurate diagnosis and assessment of treatment of acromegalic patients.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood; Diabetes Mellitus, Type 1/metabolism*
Sociodemographic determinants of glycaemic control in young diabetic patients in peninsular Malaysia

Ismail IS, Nazaimoon WM, Mohamad WB, Letchuman R, Singaraveloo M, Pendek R, et al.

Diabetes Res Clin Pract, 2000 Jan;47(1):57-69.
PMID: 10660222 DOI: 10.1016/s0168-8227(99)00104-7

Recent studies have shown that good glycaemic control can prevent the development of diabetic complications in type 1 and type 2 diabetes. We wished to observe the glycaemic control in patients from different centres in Peninsular Malaysia and the factors that determine it. We recruited 926 patients with diabetes diagnosed before age 40 years from seven different centres, with proportionate representation from the three main ethnic groups. Clinical history and physical examination were done and blood taken for HbA1c and fasting glucose. The overall glycaemic control was poor with geometric mean HbA1c of 8.6% whilst 61.1% of the patients had HbA1c greater than 8%. Glycaemic control in patients with type 2 diabetes varied between various centres and ethnic groups, with the best control obtained in Chinese patients. Significant predictors of HbA1c in both type 1 and type 2 diabetes include access to nurse educators, ethnic background and WHR. In type 2 diabetes, use of insulin was a significant predictor, while in type 1 diabetes, household income was a significant predictor. Socioeconomic status did not have a significant effect in type 2 diabetes. There were no significant differences in the glycaemic control in patients with different educational status. In conclusion, glycaemic control in big hospitals in Malaysia was poor, and was closely related to the availability of diabetes care facilities and ethnic group, rather than socioeconomic status.

Matched MeSH terms: Diabetes Mellitus, Type 1/epidemiology*; Diabetes Mellitus, Type 1/therapy*
Ethnicity and glycaemic control are major determinants of diabetic dyslipidaemia in Malaysia

Ismail IS, Nazaimoon W, Mohamad W, Letchuman R, Singaraveloo M, Hew FL, et al.

Diabet Med, 2001 Jun;18(6):501-8.
PMID: 11472471 DOI: 10.1046/j.1464-5491.2001.00494.x

AIMS: To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects.

METHODS: This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides.

RESULTS: The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol > 5.20 mmol/l, 90.9% had LDL-cholesterol > 2.60 mmol/l, 52.6% had HDL-cholesterol < 1.15 mmol/l and 27.3% had serum triglycerides > 2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist-hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia.

CONCLUSIONS: The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501-508 (2001)

Matched MeSH terms: Diabetes Mellitus, Type 1/blood; Diabetes Mellitus, Type 1/complications
Fulltext HLA-DQ A1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction

Rohana AG, Loh KC, Tin SK, Soh CH, Nazaimoon WM, Fong KY, et al.

Med J Malaysia, 2011 Jun;66(2):133-7.
PMID: 22106694

HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.

Matched MeSH terms: Diabetes Mellitus, Type 1/genetics*
Fulltext Autoimmune markers in young Malaysian patients with type 1 diabetes mellitus

Nazaimoon WM, Azmi KN, Rasat R, Ismail IS, Singaraveloo M, Wan Mohamad WB, et al.

Med J Malaysia, 2000 Sep;55(3):318-23.
PMID: 11200711

This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage.

Matched MeSH terms: Diabetes Mellitus, Type 1/immunology*
Fulltext Evaluation of antidiabetic properties of Momordica charantia in streptozotocin induced diabetic rats using metabolomics approach

Perumal, V., Khoo, W.C., Abdul-Hamid, A., Ismail, A., Saari, K., Murugesu, S., et al.

International Food Research Journal, 2015;22(3):1298-1306.
MyJurnal

Momordica charantia, also known as bitter melon or ‘peria katak’ in Malaysia, is a member of the family Cucurbitaceae. Bitter melon is an excellent source of vitamins and minerals that made it extensively nutritious. Moreover, the seed, fruit and leave of the plant contain bioactive compounds with a wide range of biological activities that have been used in traditional medicines in the treatment of several diseases, including inflammation, infections, obesity and diabetes. The aim of this study was to evaluate changes in urinary metabolite profile of the normal, streptozotocin-induced type 1 diabetes and M. charantia treated diabetic rats using proton nuclear magnetic resonance (1H-NMR) -based metabolomics profiling. Study had been carried out by inducing diabetes in the rats through injection of streptozotocin, which exhibited type 1 diabetes. M. charantia extract (100 and 200 mg/kg body weight) was administrated to the streptozotocin-induced diabetic rats for one week. Blood glucose level after administration was measured to examine hypoglycemic effect of the extract. The results obtained indicated that M. charantia was effective in lowering blood glucose level of the diabetic rats. The loading plot of Partial Least Square (PLS) component 1 showed that diabetic rats had increased levels of lactate and glucose in urine whereas normal and the extract treated diabetic rats had higher levels of succinate, creatine, creatinine, urea and phenylacetylglycine in urine. While the loading plot of PLS component 2 showed a higher levels of succinate, citrate, creatine, creatinine, sugars, and hippurate in urine of normal rat compared to the extract treated diabetic rat. Administration of M. charantia extract was found to be able to regulate the altered metabolic processes. Thus, it could be potentially used to treat the diabetic patients.

Matched MeSH terms: Diabetes Mellitus, Type 1
Fulltext Mucosal-associated invariant T cell alterations during the development of human type 1 diabetes

Gazali AM, Schroderus AM, Näntö-Salonen K, Rintamäki R, Pihlajamäki J, Knip M, et al.

Diabetologia, 2020 11;63(11):2396-2409.
PMID: 32880687 DOI: 10.1007/s00125-020-05257-7

AIMS/HYPOTHESIS: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise derivatives of bacterial riboflavin metabolites presented by MHC-Ib-related protein 1 (MR1) molecules and are important effector cells for mucosal immunity. Their development can be influenced by the intestinal microbiome. Since the development of type 1 diabetes has been associated with changes in the gut microbiome, this can be hypothesised to lead to alterations in circulating MAIT cells. Accordingly, peripheral blood MAIT cell alterations have been reported previously in patients with type 1 diabetes. However, a comprehensive analysis of the frequency and phenotype of circulating MAIT cells at different stages of type 1 diabetes progression is currently lacking.
METHODS: We analysed the frequency, phenotype and functionality of peripheral blood MAIT cells, as well as γδ T cells, invariant natural killer T (iNKT) cells and natural killer (NK) cells with flow cytometry in a cross-sectional paediatric cohort (aged 2-15) consisting of 51 children with newly diagnosed type 1 diabetes, 27 autoantibody-positive (AAb+) at-risk children, and 113 healthy control children of similar age and HLA class II background. The frequency of MAIT cells was also assessed in a separate cross-sectional adult cohort (aged 19-39) of 33 adults with established type 1 diabetes and 37 healthy individuals of similar age.
RESULTS: Children with newly diagnosed type 1 diabetes displayed a proportional increase of CD8-CD27- MAIT cells compared with healthy control children (median 4.6% vs 3.1% of MAIT cells, respectively, p = 0.004), which was associated with reduced expression of C-C chemokine receptor (CCR)5 (median 90.0% vs 94.3% of MAIT cells, p = 0.02) and β7 integrin (median 73.5% vs 81.7% of MAIT cells, p = 0.004), as well as decreased production of IFN-γ (median 57.1% vs 69.3% of MAIT cells, p = 0.04) by the MAIT cells. The frequency of MAIT cells was also decreased in AAb+ children who later progressed to type 1 diabetes compared with healthy control children (median 0.44% vs 0.96% of CD3+ T cells, p = 0.04), as well as in adult patients with a short duration of type 1 diabetes (less than 6 years after diagnosis) compared with control individuals (median 0.87% vs 2.19% of CD3+ T cells, p = 0.007). No alterations in γδ T cell, iNKT cell or NK cell frequencies were observed in children with type 1 diabetes or in AAb+ children, with the exception of an increased frequency of IL-17A+ γδ T cells in children with newly diagnosed diabetes compared with healthy control children (median 1.58% vs 1.09% of γδ T cells, p = 0.002).
CONCLUSIONS/INTERPRETATION: Changes in the frequency and phenotype of circulating MAIT cells were detectable before, at the onset and after diagnosis of type 1 diabetes in cross-sectional cohorts. Our results suggest a possible temporal association between peripheral blood MAIT cell alterations and the clinical onset of type 1 diabetes. Graphical abstract.

Matched MeSH terms: Diabetes Mellitus, Type 1
Fulltext Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro

Ghazalli N, Wu X, Walker S, Trieu N, Hsin LY, Choe J, et al.

Stem Cells Dev, 2018 07 01;27(13):898-909.
PMID: 29717618 DOI: 10.1089/scd.2017.0160

Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. In this study, we aim to identify small molecules that affect immature beta cells. A cell-based assay, using pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative reverse transcription-polymerase chain reaction analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GRflox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM d-glucose and stimulated by 17 mM d-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells.

Matched MeSH terms: Diabetes Mellitus, Type 1/metabolism
Fulltext Alteration of lipid peroxidation and antioxidant enzymes in young Malaysian IDDM patients

Indran M, Rokiah P, Chan SP, Kuppusamy UR

Med J Malaysia, 2004 Jun;59(2):166-70.
PMID: 15559165 MyJurnal

The present study was designed to explore the relationship between lipid peroxidation and antioxidant enzymes in young Malaysian insulin dependant diabetes mellitus (IDDM) patients. Indicative parameters of lipid peroxidation, activities of antioxidant enzymes and diabetes parameters were evaluated in single blood samples from 30 young type 1 diabetic patients and 30 healthy control subjects. Antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were significantly decreased while plasma malondialdehyde (MDA), an indicator for lipid peroxidation was significantly increased in IDDM patients compared to control subjects. Positive correlations between HbA1c and MDA; fasting blood glucose (FBG) and MDA and negative correlations between HbA1c and SOD; MDA and SOD were observed in these patients. No significant correlation existed between HbA1c and fasting blood glucose, GPx or CAT in the diabetic patients. The strong correlations found between lipid peroxidation, antioxidant enzymes and diabetes parameters confirms the existence of oxidative stress in our IDDM patients.

Matched MeSH terms: Diabetes Mellitus, Type 1/blood*; Diabetes Mellitus, Type 1/complications*
Fulltext Effect of Traditional Chinese Medicine Complex for diabetes (TCM-D™) on experimentally induced diabetic mice

Donald Koh Fook Chen, Joon Wah Mak, Soo Shen Ooi, Kok Fee Mak, Kwai Hoe Chong

International e-Journal of Science, Medicine & Education, 2013;7(1):4-9.
MyJurnal

We previously evaluated the biochemical changes induced by the local product TCM for diabetes (TCM-D™) on blood glucose levels and other biochemical changes in normal mice fed orally with the recommended human dose (30 ml/kg daily) and ten times this dose for eight weeks. TCM-D™ is an aqueous extract of the roots of Trichosanthes kirilowii Maxim, Paeonia lactiflora Pall, Glycyrrhiza uranlensis Fisch. and Panax ginseng Meyer (red) combined at the dry weight proportions of 36%, 28%, 18% and 18% respectively. The study showed that at these dosages the blood glucose levels as well as the body weights in treated mice were significantly reduced when compared with pretreatment values and control animals. The present study evaluated the effect of the extract in a mouse model of Type 1 diabetes mellitus.

Matched MeSH terms: Diabetes Mellitus, Type 1
Fulltext Telemedicine for the management of glycemic control and clinical outcomes of type 1 diabetes mellitus: a systematic review and meta-analysis of randomized controlled studies

Lee SWH, Ooi L, Lai YK

Front Pharmacol, 2017;8:330.
PMID: 28611672 DOI: 10.3389/fphar.2017.00330

Importance: Telemedicine has been shown to be an efficient and effective means of providing care to patients with chronic disease especially in remote and undeserved regions, by improving access to care and reduce healthcare cost. However, the evidence surrounding its applicability in type 1 diabetes remains scarce and conflicting. Objective: To synthesize evidence and quantify the effectiveness of telemedicine interventions for the management of glycemic and clinical outcomes in type 1 diabetes patients, relative to comparator conditions. Data Sources: MEDLINE, EMBASE, Cochrane Library, Web of Science, PsycINFO, and CINAHL were searched for published articles since inception until December 2016. Study Selection: Original articles reporting the results of randomized controlled studies on the effectiveness of telemedicine in people with type 1 diabetes were included. Data Extraction and Synthesis: Two reviewers independently extracted data, assessed quality, and strength of evidence. Interventions were categorized based upon the telemedicine focus (monitoring, education, consultation, case-management, and peer mentoring). Main Outcome and Measure: Absolute change in glycosylated hemoglobin A1c (HbA1c) from baseline to follow-up assessment. Results: A total of 38 studies described in 41 articles were identified. Positive effects on glycemic control were noted with studies examining telemedicine, with a mean reduction of 0.18% at the end of intervention. Studies with longer duration (>6 months) who had recruited patients with a higher baseline HbA1c (≥9%) were associated with larger effects. Telemedicine interventions that involve individualized assessments, audit with feedback and skill building were also more effective in improving glycemic control. However, no benefits were observed on blood pressure, lipids, weight, quality of life, and adverse events. Conclusions and Relevance: There is insufficient evidence to support telemedicine use for glycemic control and other clinically relevant outcome among patients with type 1 diabetes.

Matched MeSH terms: Diabetes Mellitus, Type 1

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