scholarly journals Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaoyan Tang ◽  
Liheng Meng ◽  
Ping Zhang ◽  
Xinghuan Liang ◽  
Chaozhi Dang ◽  
...  

BackgroundWe aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.MethodA Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.ResultsThe proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5–12.1%) and fasting blood glucose (FBG, 91.4–189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.ConclusionThis study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.

Diabetes Care ◽  
1980 ◽  
Vol 3 (5) ◽  
pp. 607-610 ◽  
Author(s):  
S. Howe-Davies ◽  
R. W. Simpson ◽  
R. C. Turner

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2305
Author(s):  
Röhling ◽  
Martin ◽  
Wonnemann ◽  
Kragl ◽  
Klein ◽  
...  

Background: Self-monitoring of blood glucose using capillary glucose testing (C) has a number of shortcomings compared to continuous glucose monitoring (CGM). We aimed to compare these two methods and used blood glucose measurements in venous blood (IV) as a reference. Postprandial blood glucose levels were measured after 50 g oral glucose load and after the consumption of a portion of different foods containing 50 g of carbohydrates. We also evaluated the associations between postprandial glucose responses and the clinical characteristics of the participants at the beginning of the study. Methods: 12 healthy volunteers (age: 36 ± 17 years, BMI: 24.9 ± 3.5 kg/m²) ate white bread (WB) and whole grain (WG) bread and drank a 50 g glucose drink as reference. Postprandial glucose responses were evaluated by CGM, IV and C blood glucose measurements. Incremental area under the curve (AUCi) of postprandial blood glucose was calculated for 1 h (AUCi 0-60) and 2 h (AUCi 0-120). Results: After the consumption of white bread and whole grain bread, the AUCi 0-60 min did not differ between CGM and IV or C. AUCi 0-120 min of CGM showed no difference compared to C. Correlation analyses revealed a positive association of age with glucose AUCi 0-120 (r = 0.768; P = 0.004) and WG AUCi 0-120 (r = 0.758; P = 0.004); fasting blood glucose correlated with WG AUCi 0-120 (r = 0.838; P < 0.001). Conclusion: Despite considerable inter-individual variability of postprandial glycemic responses, CGM evaluated postprandial glycemic excursions which had comparable results compared to standard blood glucose measurements under real-life conditions. Associations of AUCi 0-60 and AUCi 0-120 postprandial glucose response with age or fasting blood glucose could be shown.


2021 ◽  
Vol 12 ◽  
Author(s):  
Juyi Li ◽  
Meng Shu ◽  
Xiufang Wang ◽  
Aiping Deng ◽  
Chong Wen ◽  
...  

ObjectiveTo determine the pathogenic gene and explore the clinical characteristics of maturity-onset diabetes of the young type 2 (MODY2) pedigree caused by a mutation in the glucokinase (GCK) gene.MethodsUsing whole-exome sequencing (WES), the pathogenic gene was detected in the proband—a 20-year-old young man who was accidentally found with hyperglycemia, no ketosis tendency, and a family history of diabetes. The family members of the proband were examined. In addition, relevant clinical data were obtained and genomic DNA from peripheral blood was obtained. Pathologic variants of the candidate were verified by Sanger sequencing technology, and cosegregation tests were conducted among other family members and non-related healthy controls. After adjusting the treatment plan based on the results of genetic testing, changes in biochemical parameters, such as blood glucose levels and HAblc levels were determined.ResultsIn the GCK gene (NM_000162) in exon 9, a heterozygous missense mutation c.1160C &gt; T (p.Ala387Val) was found in the proband, his father, uncle, and grandmother. Thus mutation, which was found to co-segregate with diabetes, was the first discovery of such a mutation in the Asian population. After stopping hypoglycemic drug treatment, good glycemic control was achieved with diet and exercise therapy.ConclusionGCK gene mutation c.1160C &gt; T (p.Ala387Val) is the pathogenic gene in the GCK-MODY pedigree. Formulating an optimized and personalized treatment strategy can reduce unnecessary excessive medical treatment and adverse drug reactions, and maintain a good HbA1c compliance rate


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Yanfeng Chen ◽  
Yanwen Wang ◽  
Junzeng Zhang ◽  
Changhao Sun ◽  
Alfonso Lopez

The present study was carried out to determine the effect of berberine on glucose homeostasis and several biomarkers associated with insulin sensitivity in male Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ injection were divided into two groups. One group was used as the diabetic control and another treated by gavage feeding with 100 mg/kg/d of berberine in water containing 0.5% carboxymethyl cellulose. A group of rats without receiving STZ was used as the normal control. After 7 weeks, berberine supplementation moderately but significantly lowered fasting blood glucose levels and improved oral glucose tolerance. Berberine lowered plasma free fatty acids and C-reactive protein levels without affecting plasma insulin levels. Diabetic rats treated with berberine showed significantly lower plasma triacylglycerol and cholesterol levels. Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities. In conclusion, berberine showed a dramatic effect of lowering blood cholesterol and triacylglycerols and improved moderately glucose homeostasis in STZ-induced diabetic rats in association with multiple factors related to insulin resistance.


BMJ ◽  
1980 ◽  
Vol 280 (6223) ◽  
pp. 1148-1148
Author(s):  
S Howe-Davies ◽  
A Muir ◽  
R R Holman ◽  
R Turner

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Takumi Isaka ◽  
Hiroko Otake ◽  
Yosuke Nakazawa ◽  
...  

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.


2021 ◽  
Vol 12 (4) ◽  
pp. 1117-1128
Author(s):  
Yingkui Si ◽  
Anping Wang ◽  
Yunshuang Yang ◽  
Hongzhou Liu ◽  
Shi Gu ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3377
Author(s):  
Omorogieva Ojo ◽  
Xiao-Hua Wang ◽  
Osarhumwese Osaretin Ojo ◽  
Amanda Rodrigues Amorim Adegboye

The use of nutritional interventions for managing diabetes is one of the effective strategies aimed at reducing the global prevalence of the condition, which is on the rise. Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre. Therefore, the aim of this review was to evaluate the effects of almonds on gut microbiota, glycometabolism, and inflammatory parameters in patients with type 2 diabetes. Methods: This systematic review and meta-analysis was carried out according to the preferred reporting items for systematic review and meta-analysis (PRISMA). EBSCOhost, which encompasses the Health Sciences Research Databases; Google Scholar; EMBASE; and the reference lists of articles were searched based on population, intervention, control, outcome, and study (PICOS) framework. Searches were carried out from database inception until 1 August 2021 based on medical subject headings (MesH) and synonyms. The meta-analysis was carried out with the Review Manager (RevMan) 5.3 software. Results: Nine randomised studies were included in the systematic review and eight were used for the meta-analysis. The results would suggest that almond-based diets have significant effects in promoting the growth of short-chain fatty acid (SCFA)-producing gut microbiota. Furthermore, the meta-analysis showed that almond-based diets were effective in significantly lowering (p < 0.05) glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with type 2 diabetes. However, it was also found that the effects of almonds were not significant (p > 0.05) in relation to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and Tumour necrosis factor α, TNF-α), glucagon-like peptide-1 (GLP-1), homeostatic model assessment of insulin resistance (HOMA–IR), and fasting insulin. The biological mechanisms responsible for the outcomes observed in this review in relation to reduction in HbA1c and BMI may be based on the nutrient composition of almonds and the biological effects, including the high fibre content and the low glycaemic index profile. Conclusion: The findings of this systematic review and meta-analysis have shown that almond-based diets may be effective in promoting short-chain fatty acid-producing bacteria and lowering glycated haemoglobin and body mass index in patients with type 2 diabetes compared with control. However, the effects of almonds were not significant (p > 0.05) with respect to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and TNF-α), GLP-1, HOMA–IR, and fasting insulin.


2021 ◽  
Author(s):  
Wanlu Su ◽  
Jie Wang ◽  
Songyan Yu ◽  
Kang Chen ◽  
Wenhua Yan ◽  
...  

Abstract BackgroundThe metabolic score for insulin resistance (METS-IR) is a novel noninsulin-based metabolic index used as a substitution marker of insulin resistance. However, whether METS-IR is associated with the urinary albumin–creatinine ratio (UACR) is not well known. Therefore, we explored the associations between METS-IR and UACR and compared the discriminative ability of METS-IR and its components for elevated UACR. MethodsThis study included 37,290 subjects. METS-IR was calculated as follows: (Ln [2 × fasting blood glucose (FBG) + fasting triglyceride level (TG 0 )] × body mass index (BMI))/[Ln (high-density lipoprotein cholesterol (HDL-C))]. Participants were divided into four groups on the basis of METS-IR: <25%, 25%–49%, 50%–74%, and ≥75%. Logistic regression analyses were conducted to determine the associations between METS-IR vs. its components (FBG, TG 0 , BMI, and HDL-C) with UACR. ResultsParticipants with the highest quartile METS-IR presented a more significant trend towards elevated UACR than towards its components (odds ratio [OR]: 1.260, 95% CI: 1.152–1.378, P < 0.001 in all subjects; OR: 1.321, 95% CI: 1.104–1.579, P = 0.002 in men; OR: 1.201, 95% CI: 1.083–1.330, P < 0.001 in women). There were significant associations between METS-IR and UACR in younger participants (<65 years for women and 55–64 years for men). Increased METS-IR was significantly associated with UACR in men with FBG ≥ 5.6 mmol/L or postprandial blood glucose ≥ 7.8 mmol/L and systolic blood pressure ≥ 120 mmHg or diastolic blood pressure ≥ 80 mmHg. The relationships were significant in women with diabetes and hypertension.ConclusionsIncreased METS-IR was significantly associated with elevated UACR, and its discriminative power for elevated UACR was superior to that of its components. This findings support the clinical significance of METS-IR for evaluating renal function damage.


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