ABSTRACT
Diabetes is a major cause of end stage renal disease (ESRD), yet the natural history of diabetic kidney disease is not well understood. We aimed to identify patterns of estimated GFR (eGFR) trajectory and to determine the clinical and genetic factors and their associations of these different patterns with all-cause mortality in patients with type 2 diabetes. Among 6330 patients with baseline eGFR >60 ml/min per 1.73 m2 in the Hong Kong Diabetes Register, a total of 456 patients (7.2%) developed Stage 5 chronic kidney disease or ESRD over a median follow-up of 13 years (incidence rate 5.6 per 1000 person-years). Joint latent class modeling was used to identify different patterns of eGFR trajectory. Four distinct and non-linear trajectories of eGFR were identified: slow decline (84.3% of patients), curvilinear decline (6.5%), progressive decline (6.1%) and accelerated decline (3.1%). Microalbuminuria and retinopathy were associated with accelerated eGFR decline, which was itself associated with all-cause mortality (odds ratio [OR] 6.9; 95% confidence interval [CI]: 5.6-8.4 for comparison with slow eGFR decline). Of 68 candidate genetic loci evaluated, the inclusion of five loci (rs11803049, rs911119, rs1933182, rs11123170, and rs889472) improved the prediction of eGFR trajectories (net reclassification improvement 0.232; 95% CI: 0.057--0.406). Our study highlights substantial heterogeneity in the patterns of eGFR decline among patients with diabetic kidney disease, and identifies associated clinical and genetic factors that may help to identify those who are more likely to experience an accelerated decline in kidney function.
Subject(s)
Albuminuria/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/epidemiology , Diabetic Retinopathy/epidemiology , Kidney Failure, Chronic/epidemiology , Aged , Albuminuria/pathology , Albuminuria/physiopathology , Asian People , Cause of Death , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/mortality , Diabetic Nephropathies/genetics , Diabetic Nephropathies/pathology , Diabetic Nephropathies/physiopathology , Diabetic Retinopathy/genetics , Disease Progression , Female , Follow-Up Studies , Genetic Loci/genetics , Glomerular Filtration Rate , Hong Kong/epidemiology , Humans , Incidence , Kidney/physiopathology , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Prospective Studies , Registries/statistics & numerical dataABSTRACT
AIMS: We evaluated the effect of personalized risk counseling incorporating clinical and genetic risk factors on patient empowerment and risk factor control in diabetes. METHODS: Patients with type 2 diabetes (T2D) with suboptimal glycaemic control (HbA1c ≥ 7.5%) were randomized to a genetic counselling (GC) or control group. All patients underwent genetic testing for alleles at three loci associated with diabetic complications. The GC group received additional explanation of the joint associations of genetic and modifiable risk factors on risk of complications. All patients were reassessed at 12 months including validated questionnaires for patient reported outcomes. The primary outcome was proportion of patients reaching ≥ 3 of 5 predefined treatment targets (HbA1c < 7%, BP < 130/80 mmHg, LDL-C < 2.6 mmol/L, Triglyceride < 2.0 mmol/L, use of renin-angiotensin system inhibitors). Secondary outcomes included new-onset chronic kidney disease or microalbuminuria and patient reported outcome measures. RESULTS: A total of 435 patients were randomized and 420 patients were included in the modified intention-to-treat analysis. At 12 months, the proportion of patients who attained ≥ 3 targets increased from 41.6% to 52.3% in the GC group (p = 0.007) versus 49.5% to 62.6% in the control group (p = 0.003), without between-group difference. Both groups had similar reduction in HbA1c, LDL-C and increased use of medications. In per protocol analysis, the GC group had higher diabetes empowerment, with reduced diabetes distress. In the GC group, the greatest improvement in positive attitude and self-care activities was observed in the intermediate to high genetic risk score (GRS) groups. CONCLUSIONS: In patients with T2D receiving integrated care, additional counselling on genetic risk of complications did not further improve risk factor control, although the improvement in self-efficacy warrants long-term evaluation.
Subject(s)
Delivery of Health Care, Integrated , Diabetes Mellitus, Type 2 , Cholesterol, LDL , Counseling , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/therapy , Genetic Testing , Glycated Hemoglobin/analysis , Humans , Patient ParticipationABSTRACT
Diabetes has become a major burden of healthcare expenditure. Diabetes management following a uniform treatment algorithm is often associated with progressive treatment failure and development of diabetic complications. Recent advances in our understanding of the genomic architecture of diabetes and its complications have provided the framework for development of precision medicine to personalize diabetes prevention and management. In the present review, we summarized recent advances in the understanding of the genetic basis of diabetes and its complications. From a clinician's perspective, we attempted to provide a balanced perspective on the utility of genomic medicine in the field of diabetes. Using genetic information to guide management of monogenic forms of diabetes represents the best-known examples of genomic medicine for diabetes. Although major strides have been made in genetic research for diabetes, its complications and pharmacogenetics, ongoing efforts are required to translate these findings into practice by incorporating genetic information into a risk prediction model for prioritization of treatment strategies, as well as using multi-omic analyses to discover novel drug targets with companion diagnostics. Further research is also required to ensure the appropriate use of this information to empower individuals and healthcare professionals to make personalized decisions for achieving the optimal outcome.
Subject(s)
Diabetes Mellitus/classification , Diabetes Mellitus/therapy , Disease Management , Precision Medicine/classification , Precision Medicine/methods , Diabetes Mellitus/diagnosis , Humans , Pharmacogenetics/classification , Pharmacogenetics/methods , Risk FactorsABSTRACT
OBJECTIVE: To study the polymorphism of HLA-DM gene in Cantonese patients with condyloma acuminata(CA) and determine the susceptible genetic factors of CA. METHODS: DMA and DMB typing was performed in 98 Cantonese patients with CA and 93 healthy controls using restriction fragment length polymorphism method. RESULTS: The gene frequencies of DMA*0101 and DMB*0101 were significantly higher in the patients than in the controls (P<0.05 and P<0.01, respectively), and gene frequency of DMA*0102 was lower in patients than in the controls (P<0.01). Genotype frequencies of HLA-DM showed no significant difference between CA patients and the controls (P>0.05). CONCLUSION: DMA*0101 and DMB*0101 alleles may be the susceptibility genes or closely linked to the susceptibility gene in Cantonese patients with CA.