We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).
In 5,230 Chinese patients ...(47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 interquartile range 1, 12 years), enrolled consecutively in 1996-2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.
At baseline, 28.6% (n = 1,494) had low CP (<200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15-1.84, P = 0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12 vs. -1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10-1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04-1.83, P = 0.024) in the GADA+ group.
There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.
Aims: Prediabetes is defined by HbA1c, fasting (FPG) and 2-hour plasma glucose (2h-PG) during 75 gram oral glucose test (OGTT) although these values often show poor concordance. Most diabetes ...prevention trials involved people with impaired glucose tolerance (IGT) diagnosed as 2h-PG 7.8-11.0 mmol/L. Continuous glucose monitoring (CGM) may detect early dysglycemia especially postprandial glucose excursions. We examined correlations amongst HbA1c, FPG, 1-h and 2h-PG during OGTT and CGM metrics in individuals with IGT.
Methods: 85 Chinese with IGT (mean±SD age 57±8 years, 51 (60%) female, BMI 26.6±4.0 kg/m2) participating in a lifestyle modification study had measurement of HbA1c, PG during 75g OGTT and 14-day CGM metrics (Freestyle Libre, Abbott) during a 3-week period at baseline. We examined their correlations using Spearman coefficients.
Results: The mean HbA1c was 5.8±0.3 %, FPG 5.3±0.4 mmol/L, 1h-PG 11.0±1.6 mmol/L and 2h-PG 8.5±1.3 mmol/L. For CGM, the mean glucose management index (GMI) was 5.9±0.2 % and time in tight glycemic range (TITR 3.9-7.8 mmol/L) was 86.7±6.6 %. There was a tendency for HbA1c (r=0.587, p=0.097) to correlate with GMI and negatively with TITR (r=-0.644, p=0.061). The respective correlates between FPG and GMI was r=0.623 (p=0.073) and that between FPG and TITR was r=-0.559 (p=0.118). There was weak correlation between 1h-PG and CGM time above range >7.8 mmol/L (r=0.301, p=0.43). There was no correlation amongst 1h-PG, 2h-PG with HbA1c and other conventional CGM metrics.
Conclusions: In individuals with IGT, HbA1c and FPG showed better correlations with CGM metrics of average glycemia than PG values during OGTT. Future studies are needed to define the use of CGM and appropriate metrics in detection of IGT.
Disclosure
E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. J.He: None. N.Chu: None. E.W.M.Poon: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd.
Funding
Health and Medical Research Fund (17180431)
The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of ...lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria
Lactobacillus
and
Bifidobacterium
as well as suppress the potentially pathogenic bacteria
Escherichia coli
. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes
via
actions on the gut microbiota.
Extensive loss of natural wetlands caused by changes in land use largely diminishes the food resources essential for the survival of migratory waterbirds. Globally, the decline in waterbird ...populations in East Asia is the most serious, with 64% of these populations showing a decreasing trend. In this study, we applied DNA metabarcoding to examine the spatiotemporal variations and diversities in the dietary compositions of migratory waterbirds in a natural/artificial wetland complex in Asia. By investigating 110 fecal samples from the endangered black-faced spoonbill (Platalea minor) wintering in the wetland, our results show that P. minor had a broad dietary spectrum. The birds fed on at least 26 species in the classes Actinopterygii and Malacostraca, with Mugiliformes, Cichliformes, and Gobiiformes being the main taxa in their diets. Our results also demonstrated clear patterns of the spatiotemporal variations between the roosting groups and intraspecific variations between the individuals, which potentially reflect some of their feeding habits, and the probable usage of different habitat types in the wetland complex. Using high-throughput sequencing, we were able to elucidate the food resources that are critical to P. minor non-invasively, this method can also be used to provide invaluable information for the conservation of many other waterbird species.
Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to ...rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.
Background: Young-onset diabetes (YOD) is heterogenous in aetiologies and clinical phenotypes. The PRISM study is a 3-year randomised controlled trial to evaluate the effect of precision treatment ...algorithm guided by biogenetic information on clinical outcomes in Chinese with YOD.
Methods: In 2020-2021, we randomized 884 Chinese (18-50 years) with non-type 1 diabetes diagnosed ≤40 years to PRISM (n=443) or usual care (n=441). The PRISM group underwent assessment including biogenetic markers (anti-glutamic acid decarboxylase antibody GADA, C-peptide, monogenic diabetes gene mutations and genetic risk scores predicting YOD, insulin requirement and complications) for issue of a personalized report to guide multidisciplinary care comprising endocrinologist consultation, counselling, empowerment on self-care, and reminders by supporting staff for 1 year at the Diabetes Research Centre before return to usual care. All patients return for assessment at year 3 for ascertainment of all-diabetes related endpoints.
Results: Amongst 884 patients (mean±SD: age 40.7±6.5 years, median IQR age at diagnosis 34 29,38 years, disease duration 7 3,12 years, HbA1c 7.5±1.7%, 96.2% on glucose-lowering drugs, 27.7% on insulin), 74.7% had family history (19.7% both parents affected), 66.7% hypertension, 76.4% dyslipidaemia, 83% overweight and 35.4% albuminuria. Median fasting C-peptide was 0.6 (0.4, 0.9) nmol/L, 9.5% had C-peptide <0.2 nmol/L, 5.1% were GADA positive. In the PRISM group, 21.9% had low birthweight, 50.7%, childhood obesity, 5.7%, steroid exposure in childhood, 1.8-17.3%, co-existing endocrinopathies (thyroid disease, Cushing’s syndrome, polycystic ovarian syndrome), 7.5%, thalassaemia trait, 7.1%, chronic hepatitis B infection and 10.3%, mental illness.
Conclusions: Lifecourse factors, endocrinopathies and mental illnesses are prevalent in YOD.
Disclosure
A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. Y.Fan: None. B.Fan: None. C.K.P.Lim: Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. E.W.M.Poon: None. S.T.F.Tsoi: None. R.Ozaki: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk.
Funding
Health and Medical Research Fund (CFS-CUHK2)
One of the major threats for the massive loss in global amphibian diversity is chytridiomycosis, caused by chytrid fungi Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal). Following ...its discovery in 2013, Bsal has emerged as a severe threat to the global survival of urodelans. In 2018, a study reported a high prevalence of Bsal (65.6%) in the Hong Kong newts (Paramesotriton hongkongensis, Near Threatened) of a southern China population adjacent to Hong Kong (HK). Uncertainty regarding the Bsal infection status of P. hongkongensis inhabiting HK raised deep concern over the risk of introducing Bsal from that population. We screened the skin swabs from wild individuals of P. hongkongensis, 15 sympatric amphibian species, and 16 imported amphibian species in HK for chytrids. We found that both Bsal and Bd occur in low prevalences in P. hongkongensis (Bsal 1.7%, 5/293; Bd 0.34%, 1/293), Hong Kong cascade frog, Amolops hongkongensis, family Ranidae (Bsal only, 5.26%, 1/19), and Asian common toad, Duttaphrynus melanostictus, family Bufonidae (Bsal only, 5.88%, 1/17), populations of HK, with infected individuals being asymptomatic, suggesting a potential role of these species as reservoirs of Bsal. Conversely, Bd, but not Bsal, was present on 13.2% (9/68) of imported amphibians, indicating a high chytrid introduction risk posed by international amphibian trade. Long-term surveillance of the presence of Bd and Bsal in wild and captive amphibians would be advisable, and we recommend that import and export of nonnative chytrid carriers should be prevented, especially to those regions with amphibian populations naïve to Bd and Bsal.
IntroductionType 2 diabetes is preventable in subjects with impaired glucose tolerance based on 2-hour plasma glucose (2hPG) during 75 g oral glucose tolerance test (OGTT). We incorporated routine ...biochemistry to improve the performance of a non-invasive diabetes risk score to identify individuals with abnormal glucose tolerance (AGT) defined by 2hPG≥7.8 mmol/L during OGTT.Research design and methodsWe used baseline data of 1938 individuals from the community-based “Better Health for Better Hong Kong - Hong Kong Family Diabetes Study (BHBHK-HKFDS) Cohort” recruited in 1998–2003. We incorporated routine biochemistry in a validated non-invasive diabetes risk score, and evaluated its performance using area under receiver operating characteristics (AUROC) with internal and external validation.ResultsThe AUROC of the original non-invasive risk score to predict AGT was 0.698 (95% CI, 0.662 to 0.733). Following additional inclusion of fasting plasma glucose, serum potassium, creatinine, and urea, the AUROC increased to 0.778 (95% CI, 0.744 to 0.809, p<0.001). Net reclassification improved by 31.9% (p<0.001) overall, by 30.8% among people with AGT and 1.1% among people without AGT. The extended model showed good calibration (χ2=11.315, p=0.1845) and performance on external validation using an independent data set (AUROC=0.722, 95% CI, 0.680 to 0.764).ConclusionsThe extended risk score incorporating clinical and routine biochemistry can be integrated into an electronic health records system to select high-risk subjects for evaluation of AGT using OGTT for prevention of diabetes.
Introduction
To compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus ...neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM).
Methods
This was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (
n
= 23) versus NPH (
n
= 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4–6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24.
Results
HbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c < 7% without confirmed hypoglycemia. There were no differences in anytime glucose SD at week 24 (LS mean difference − 0.08 mmol/l, 95% CI − 0.42–0.26,
p
= 0.63). Anytime %TIRs (3.9–10.0 mmol/l) at week 24 were similar (
p
= 0.91). Nocturnal % time below range < 3.9 mmol/l was significantly lower in the Gla-300 group (least squares (LS) mean difference – 5.03% − 9.92 to − 0.14,
p
= 0.04) with lower % coefficient of variation (LS mean difference − 4.5% − 8.1 to − 0.8,
p
= 0.018). Diurnal TIR was higher in Gla-300 patients at week 11 but there were no differences at week 24.
Conclusions
Once-daily bedtime Gla-300 was associated with lower nocturnal GV, time below range and self-reported hypoglycemia in insulin-naïve Chinese T2D patients over a 24-week study period, as compared with NPH insulin.
Clinical Trial Registration
ClinicalTrials.gov Identifier: NCT03389490.
During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for ...approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations. This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to consider premarket approval. Data sources were verbatim transcripts available publicly from the FDA. Number of words spoken, directionality of votes on device approval, profession, and demographics were collected. 658,954 words spoken by 536 members during 49 meetings of 11 Panels were analyzed. Based on multivariate analysis, biostatisticians spoke more (+373 words; P = 0.0002), and women (-187 words; P = 0.0184) and other non-physician voting members less (-213 words; P = 0.0306), than physicians. Speaking more was associated with abstaining (P = 0.0179), and with voting against the majority (P = 0.0153). Non-physician, non-biostatistician members (P = 0.0109), and those having attended more meetings as a voting member (P = 0.0249) were more likely to vote against approval. In bivariable analysis, unanimous Panels had a greater proportion of biostatisticians (mean 0.1580; 95% CI 0.1237-0.1923) than non-unanimous Panels (0.1107; 95% CI 0.0912-0.1301; p = 0.0201). Panelists likely to vote against the majority include non-physician, non-biostatisticians; experienced Panelists; and more talkative members. The increased presence of biostatisticians on Panels leads to greater voting consensus. Having a diversity of opinions on Panels, including in sufficient numbers those members likely to dissent from majority views, may help ensure that a diversity of opinions are aired before decision-making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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