scholarly journals Understanding Metabolic Memory: The Prolonged Influence of Glycemia During the Diabetes Control and Complications Trial (DCCT) on Future Risks of Complications During the Study of the Epidemiology of Diabetes Interventions and Complications (EDIC)

2021 ◽  
Author(s):  
John M. Lachin ◽  
David M. Nathan ◽  
the DCCT/EDIC Research Group
Keyword(s):  
Conventional Therapy ◽  
Microvascular Complications ◽  
Intensive Therapy ◽  
Diabetes Control ◽  
Metabolic Memory ◽  
Beneficial Effects ◽  
Legacy Effect ◽  
Hba1c Levels ◽  
Diabetes Interventions

The Diabetes Control and Complications Trial (DCCT, 1983-1993) showed that intensive therapy (mean HbA1c 7.2%) compared with conventional therapy (mean HbA1c 9.0%) markedly reduced the risks of retinopathy, nephropathy and neuropathy, and these reductions in complications were entirely attributable, statistically, to the difference in mean HbA1c levels. The DCCT cohort has been followed in the Epidemiology of Diabetes Interventions and Complications study (EDIC, 1994 to date). <p>Early in EDIC, mean HbA1c levels in the former intensively and conventionally treated groups converged. Nevertheless, the beneficial effects of DCCT intensive versus conventional therapy on microvascular complications not only persisted but increased during EDIC. The differences in complications during EDIC were wholly explained, statistically, by differences between groups in HbA1c levels during DCCT. These observations give rise to the concept of metabolic memory. Subsequent similar findings from the UKPDS gave rise to a similar concept, which they called the legacy effect. </p> <p>In this report, we present the evidence to support metabolic memory as both a biological and epidemiological phenomenon, and discuss potential underlying mechanisms. We also compare metabolic memory and the legacy effect and conclude that the two are likely biologically similar, with comparable effects on long-term outcomes.</p> <p>The long-term influence of metabolic memory on the risk of micro- and macrovascular complications supports the implementation of intensive therapy, with the goal of maintaining near normal levels of glycemia, as early and as long as safely possible in order to limit the risk of complications.</p>

scholarly journals Understanding Metabolic Memory: The Prolonged Influence of Glycemia During the Diabetes Control and Complications Trial (DCCT) on Future Risks of Complications During the Study of the Epidemiology of Diabetes Interventions and Complications (EDIC)

2021 ◽  
Author(s):  
John M. Lachin ◽  
David M. Nathan ◽  
the DCCT/EDIC Research Group
Keyword(s):  
Conventional Therapy ◽  
Microvascular Complications ◽  
Intensive Therapy ◽  
Diabetes Control ◽  
Metabolic Memory ◽  
Beneficial Effects ◽  
Legacy Effect ◽  
Hba1c Levels ◽  
Diabetes Interventions

The Diabetes Control and Complications Trial (DCCT, 1983-1993) showed that intensive therapy (mean HbA1c 7.2%) compared with conventional therapy (mean HbA1c 9.0%) markedly reduced the risks of retinopathy, nephropathy and neuropathy, and these reductions in complications were entirely attributable, statistically, to the difference in mean HbA1c levels. The DCCT cohort has been followed in the Epidemiology of Diabetes Interventions and Complications study (EDIC, 1994 to date). <p>Early in EDIC, mean HbA1c levels in the former intensively and conventionally treated groups converged. Nevertheless, the beneficial effects of DCCT intensive versus conventional therapy on microvascular complications not only persisted but increased during EDIC. The differences in complications during EDIC were wholly explained, statistically, by differences between groups in HbA1c levels during DCCT. These observations give rise to the concept of metabolic memory. Subsequent similar findings from the UKPDS gave rise to a similar concept, which they called the legacy effect. </p> <p>In this report, we present the evidence to support metabolic memory as both a biological and epidemiological phenomenon, and discuss potential underlying mechanisms. We also compare metabolic memory and the legacy effect and conclude that the two are likely biologically similar, with comparable effects on long-term outcomes.</p> <p>The long-term influence of metabolic memory on the risk of micro- and macrovascular complications supports the implementation of intensive therapy, with the goal of maintaining near normal levels of glycemia, as early and as long as safely possible in order to limit the risk of complications.</p>

scholarly journals Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

2016 ◽  
Vol 113 (21) ◽  
pp. E3002-E3011 ◽  
Author(s):  
Zhuo Chen ◽  
Feng Miao ◽  
Andrew D. Paterson ◽  
John M. Lachin ◽  
Lingxiao Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Conventional Therapy ◽  
Therapy Group ◽  
Intensive Therapy ◽  
Metabolic Memory ◽  
Blood Monocytes ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Beneficial Effects

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16–17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.

Beyond the Diabetes Control and Complications Trial—Addressing Weight Gain in Type 1 Diabetes

2008 ◽  
Vol 04 (01) ◽  
pp. 62 ◽  
Author(s):  
Jonathan Purnell
Keyword(s):  
Type 1 Diabetes ◽  
Weight Gain ◽  
Microvascular Complications ◽  
Intensive Therapy ◽  
Diabetes Control ◽  
Controlled Clinical Trial ◽  
Normal Range ◽  
Randomised Controlled ◽  
Blood Glucose Concentrations

The Diabetes Control and Complications Trial (DCCT) was a prospective, randomised, controlled clinical trial that began in the 1980s and was carried out over a decade to determine whether intensive treatment aimed at maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of microvascular complications in patients with type 1 diabetes. The results showed that intensive therapy effectively delays the onset and progression of diabetic retinopathy, nephropathy, and neuropathy in patients with type 1 diabetes.1The side effects associated with intensive therapy were a nearly three-fold increased frequency of severe hypoglycaemia and greater weight gain. For the majority of patients with type 1 diabetes, the benefits of intensive therapy were considered to vastly outweigh these risks. However, the potential detrimental effects of weight gain, especially on macrovascular risks, are being revisited.

Microvascular complications: DCCT/EDIC, Pittsburgh, and Finland

2016 ◽  
Author(s):  
David Levy
Keyword(s):  
Diabetes Complications ◽  
Severe Hypoglycaemia ◽  
Microvascular Complications ◽  
Good Control ◽  
Good Glycaemic Control ◽  
Legacy Effect ◽  
End Stage ◽  
Intensive Control ◽  
Long Term Mortality

The progression of microvascular complications is documented in the three-decade Diabetes Control and Complications Trial (DCCT), its follow-on, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, and two non-interventional studies, the Pittsburgh Epidemiology of Diabetes Complications study (EDC) and FinnDiane. The DCCT is described in detail. DCCT confirmed that good glycaemic control (A1C 7% (53 mmol/mol)) for 7 years reduced the risk of microvascular complications by 50–75% compared with A1C of 9% (75). Severe hypoglycaemia associated with improved glycaemia, is not seen in recent studies, probably due to increasing expertise in managing intensive control. Good control has a long legacy effect, and has recently been shown to reduce long-term mortality. End-stage microvascular complications occur in 1% or fewer. Glycaemia accounts for nearly all the differences in risk of microvascular complications. Other studies identify a persistent A1C 9% or more as a major risk for advanced tissue complications.

Are School Nurses Using the Recommendations of the Diabetes Control and Complications Trial in the Care of Students with Diabetes?

2002 ◽  
Vol 18 (3) ◽  
pp. 138-143 ◽  
Author(s):  
Monica Blum
Keyword(s):  
Quality Of Life ◽  
Chronic Diseases ◽  
Americans With Disabilities Act ◽  
Intensive Therapy ◽  
School Nurses ◽  
Diabetes Control ◽  
Large Numbers

Diabetes is one of the most common chronic diseases of childhood. It is listed as a disabling condition under the Americans with Disabilities Act, and therefore accommodations must be made for these children in school. School nurses are responsible for large numbers of children, usually in more than one setting. The Diabetes Control and Complications Trial examined intensive therapy and its effects on the long-term morbidity and quality of life of diabetic adolescents. A number of recommendations were made that apply to school nurses. The purpose of this article is to determine if any studies have been conducted to explore whether school nurses are using the results of the Diabetes Control and Complications Trial to write individualized healthcare plans defining the care of students with diabetes.

scholarly journals Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

2022 ◽  
Author(s):  
Edward J. Boyko ◽  
Leila R. Zelnick ◽  
Barbara H. Braffett ◽  
Rodica Pop-Busui ◽  
Catherine C. Cowie ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Lower Extremity ◽  
Risk Reduction ◽  
Significant Risk ◽  
Diabetes Control ◽  
Cox Models ◽  
Intensive Glycemic Control ◽  
Causal Pathway ◽  
Diabetes Interventions

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces risk of lower extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m<sup>2</sup>, albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (p<0.05).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>

Sign in / Sign up

Export Citation Format

Share Document