Neurocognitive outcomes in young adults with early-onset type 1 diabetes: a prospective follow-up study

OBJECTIVE

The aim of this study was to reexamine the neurocognitive function of a cohort of young adults with early-onset type 1 diabetes and compare their cognitive function to a matched control group. We also examined whether cognitive function was related to prospectively obtained severe hypoglycemia history, long-term glycemic control, or severe diabetic ketoacidosis.

RESEARCH DESIGN AND METHODS

Testing included Wechsler Intelligence Scale for Children and Adults, Wechsler Memory Scale, Cattell Culture Fair Intelligence Test (CCFIT), Wisconsin Card Sorting Test (WCST), youth and adult self-report, and Beck Depression Inventory. We tested 34 control subjects (mean ± SE, age 19.5 ± 0.5 years) and 33 type 1 diabetic subjects (age 19.3 ± 0.5 years, age at type 1 diabetes onset 3.3 ± 0.3 years, A1C from diagnosis 8.7 ± 0.1%, and diabetes duration 16.0 ± 0.5 years).

RESULTS

There was no difference in full-scale IQ scores in type 1 diabetic and control subjects (100.7 ± 2.0 vs. 102.5 ± 1.4). There was no difference between groups in memory subtests or in reporting of emotional and behavioral difficulties. The type 1 diabetes group scored lower on the CCFIT for fluid intelligence compared with control subjects (P = 0.028) and also scored lower on WCST with more perseverative errors (P = 0.002) and fewer categories completed (P = 0.022).

CONCLUSIONS

These data suggest no difference in general intellectual ability, memory, and emotional difficulties in our cohort of young adults with early-onset type 1 diabetes compared with control subjects and no deterioration over time. There were, however, findings to suggest subtle changes leading to poorer performance on complex tasks of executive function.The impact of type 1 diabetes on the developing brain remains controversial. Earlier age of diabetes onset has long been identified as one of the strongest risk factors associated with cognitive dysfunction, ranging from poorer performance on general intellectual testing (1,2) to specific deficits with visuospatial tasks, attention, and psychomotor efficiency. The effect of early-onset diabetes, however, is confounded by the impact of recurrent severe hypoglycemia. Repeated severe hypoglycemia has been reported to adversely affect various cognitive domains, in particular long-term memory, attention, and verbal IQ, although this has not been consistent across studies (3,4). Moreover, many of these studies are limited by their retrospective collection of hypoglycemia history.We previously reported neurocognitive outcomes in 84 children with early-onset diagnosis of type 1 diabetes defined as type 1 diabetes onset before 6 years of age (4). In that initial study, we compared those subjects who had a history of early severe hypoglycemia with those who had a history of late severe hypoglycemia and also compared those who had experienced severe hypoglycemia with peers who had no history of seizures. Surprisingly, there were no group differences revealed on intellectual, memory, or behavioral measures. Furthermore, there was no evidence that episodes of seizure or coma, even those occurring in early childhood, resulted in broad cognitive dysfunction, nor was there evidence of specific memory difficulties at the time of testing.In this study, we reevaluate the neurocognitive function of the cohort—with onset of type 1 diabetes before age 6 years—now that they are young adults. This early-onset type 1 diabetes cohort is unique in that all subjects were initially recruited from a population-based cohort and have been prospectively followed from diagnosis with documentation of hypoglycemia rates and other key clinical data, including A1C, at regular 3-month clinic visits.Our aims were, first, to determine whether there had been any deterioration in neurocognitive function in this population-based cohort of young adults with early-onset type 1 diabetes over the 10 years since they were previously tested. Second, we sought for the first time to compare the neurocognitive outcomes of this cohort to a group of age- and sex-matched healthy young adults. Finally, we aimed to determine whether cognitive function in this cohort of patients with early-onset type 1 diabetes was related to their severe hypoglycemia history, long-term glycemic control, or history of severe diabetic ketoacidosis.     

Complications and cardiovascular risk factors in South Asians and Europeans with early-onset type 2 diabetes

BACKGROUND: Type 2 diabetes is a major cardiovascular risk factor, and early-onset (<40 years) type 2 diabetes is becoming more common. AIM: To determine the prevalence of complications, and cardiovascular risk factors at diagnosis, in early-onset type 2 diabetes, and to compare these between South Asians and Europeans. DESIGN: Prospective study of newly-diagnosed type 2 diabetes patients aged <40 years, attending hospital and primary care clinics 1999-2001. METHODS: Patients were assessed for signs of macrovascular disease, retinopathy, neuropathy and nephropathy. Cardiovascular risk factors were also determined. RESULTS: Overall, 292 patients were enrolled (165 South Asians). Macrovascular disease was more prevalent in South Asians (15.7% vs. 9.4%, p<0.001), as was microvascular disease (27.3% vs. 16.5%, p<0.001), including retinopathy (17.5% vs. 7.9%, p<0.001), and nephropathy (18.1% vs. 7.8%, p<0.001). South Asians had trends towards greater waist:hip ratio (0.95 vs. 0.90), and higher blood pressure (127/80 vs. 123/76 mmHg). HDL cholesterol was lower (1.0 vs. 1.3 mmol/l, p<0.001) and fasting triglycerides higher (1.9 vs. 1.5 mmol/l, p<0.001) in South Asians. Absolute CHD risk was significantly higher in South Asians (16.9% vs. 13.7%, p<0.001). DISCUSSION: Complications were common at diagnosis, with a quarter of all patients having evidence of at least one diabetic complication. South Asians had a higher prevalence of established macrovascular and microvascular disease, compared to Europeans, and a higher risk of CHD, predominantly because of lower HDL cholesterol and higher blood pressure.     

Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes

OBJECTIVE: Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial. RESEARCH DESIGN AND METHODS: A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18-45 years and not treated with permanent insulin for < or =6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1 alpha (HNF-1 alpha) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1 alpha gene. RESULTS: A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a beta-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1 alpha mutations, the novel missense mutation A501T, and the previously reported R583Q. CONCLUSIONS: This unselected series shows that there is considerable heterogeneity in apparent YT2D. beta-Cell autoantibodies should be performed in all those presenting at ages 18-45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.     

Management of type 2 diabetes in youth: an update

Although type 1 diabetes historically has been more common in patients eight to 19 years of age, type 2 diabetes is emerging as an important disease in this group. Type 2 diabetes accounts for 8 to 45 percent of new childhood diabetes. This article is an update from the National Diabetes Education Program on the management of type 2 diabetes in youth. High-risk youths older than 10 years have a body mass index greater than the 85th percentile for age and sex plus two additional risk factors (i.e., family history, high-risk ethnicity, acanthosis nigricans, polycystic ovary syndrome, hypertension, or dyslipidemia). Reducing overweight and impaired glucose tolerance with increased physical activity and healthier eating habits may help prevent or delay the development of type 2 diabetes in high-risk youths. The American Academy of Pediatrics does not recommend population-based screening of high-risk youths; however, physicians should closely monitor these patients because early diagnosis may be beneficial. The American Diabetes Association recommends screening high-risk youths every two years with a fasting plasma glucose test. Patients diagnosed with diabetes should receive self-management education, behavior interventions to promote healthy eating and physical activity, appropriate therapy for hyperglycemia (usually metformin and insulin), and treatment of comorbidities.     

Redefining relationships and identity in young adults with type 1 diabetes

Title.  Redefining relationships and identity in young adults with type 1 diabetes.
Aim.  This paper is a report of a study exploring the meaning of interactions with and supports of self-management from parents and other significant others for young adults with type 1 diabetes.
Background.  Adolescence and young adulthood is known to be a critical period for people living with diabetes in terms of diabetes control, which is why support from significant others is of utmost importance during the transition to adult life.
Method.  A grounded theory approach was used. Interviews with 13 young adults with type 1 diabetes and 13 parents 2 years after transfer to adult diabetes care were conducted during 2006–2007. Internet communication between young people on a diabetes website was also included in the constant comparative analysis.
Findings.  Transition to adult life for young adults with diabetes was characterized by a relational and reflexive process leading to ongoing redefinition of relationships and identity. Parents were perceived as the most reliable supporters, compared to partners, siblings and other significant others. Chat friends can also become important through emotional, social and diabetes-related support in internet communication. The young adults showed growing awareness of their own capacities, shortcomings and emotional reactions, reflections which contribute to a redefinition of self.
Conclusion.  Further research is needed to explore how contemporary interactions contribute to development of the self. By focusing on supporting relationships, nurses are in a strategic position to develop knowledge and modify clinical programmes that promote diabetes management and care by taking supporting interactions into account from a contemporary point of view.     

Complications and comorbidities as influencing factors of health outcomes in older adults with type 2 diabetes mellitus

BackgroundComplications and comorbidities might increase medical burdens and lead to poor health outcomes among people aged 65 years and older who suffer from type 2 diabetes mellitus (T2DM).AimThe aim of this study was to investigate whether the presence of complications and comorbidities was associated with poor health outcomes among older adults with T2DM.MethodsA cross-sectional study was conducted in an outpatient endocrinology department of a teaching hospital in Taiwan. In total, 577 community-dwelling participants with T2DM aged 65 years and older were recruited. Health outcomes were measured by a body composition analyser, a blood biochemical examination, and structured self-reported questionnaires, including the Mini Nutritional Assessment, Activities of Daily Living, Healthy Diet Behaviour, International Physical Activity Questionnaire, and self-reported complications (retinopathies, nephropathies, neuropathies, and foot problems) and comorbidities (hypertension, hyperlipidaemia, heart diseases, and sarcopenia).ResultsParticipants' average age was 73.94 ± 6.73 years. Participants with complications exhibited significantly decreased levels of self-rated health (β = −0.09) and significantly higher sedentary times (β = 0.13). Participants with complications (β = −0.14) and sarcopenia (β = −0.13) had significantly decreased levels of activities of daily living. Participants with complications (β = −0.06) and hyperlipidaemia (β = −0.19) had significantly decreased muscle strength. Participants with complications (odds ratio (OR [95% confidence interval]): 0.46 [0.29, 0.72]) and hypertension (OR: 0.64 [0.42, 0.99]) had significantly lower odds of falling in the past year.ConclusionsComplications and comorbidities are important factors affecting health outcomes among older adults with T2DM. Complications and hypertension, hyperlipidaemia, and sarcopenia might lead to poor subjective and objective health outcomes. This study makes suggestions for policymakers and clinical health professionals as to the importance of monitoring and preventing complications and comorbidities.     

Poor prognosis of young adults with type 1 diabetes: a longitudinal study

OBJECTIVE: To determine the role of early behavioral and psychological factors on later outcomes in young adults with childhood- or adolescent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a longitudinal cohort study of patients recruited from the register of the young adult outpatient diabetes clinic, Oxford, U.K. A total of 113 individuals (51 male subjects) aged 17-25 years completed assessments, and 87 (77%) were reinterviewed as older adults (aged 28-37 years). Longitudinal assessments were made of glycemic control (HbA(1c)) and complications. Psychological state at baseline was assessed using the Present State Examination and self-report Symptom Checklist, with corresponding interview schedules administered at follow-up. RESULTS: There was no significant improvement between baseline and follow-up in mean HbA(1c) levels (8.5 vs. 8.6% in men, 9.3 vs. 8.7% in women). The proportion of individuals with serious complications (preproliferative or laser-treated retinopathy, proteinuria or more severe renal disease, peripheral neuropathy, and autonomic neuropathy) increased from 3-37% during the 11-year period. Women were more likely than men to have multiple complications (23 vs. 6%, difference 17%, 95% CI 4-29%, P = 0.02). Psychiatric disorders increased from 16 to 28% (20% in men, 36% in women at follow-up, difference NS), and 8% had psychiatric disorders at both assessments. Baseline psychiatric symptom scores predicted follow-up scores (beta = 0.32, SE [beta] 0.12, P = 0.008, 95% CI 0.09-0.56) and recurrent admissions with diabetic ketoacidosis (odds ratio 9.1, 95% CI 2.9-28.6, P < 0.0001). CONCLUSIONS: The clinical and psychiatric outcome in this cohort was poor. Psychiatric symptoms in later adolescence and young adulthood appeared to predict later psychiatric problems.     

Awareness and treatment of dyslipidemia in young adults with type 1 diabetes

OBJECTIVE: Dyslipidemia is a preventable major risk factor for coronary heart disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is known concerning awareness and adequacy of dyslipidemia treatment in this population. In this report, we describe the prevalence of dyslipidemia and adequacy of pharmacological treatment in patients with type 1 diabetes and comparable nondiabetic subjects. RESEARCH DESIGN AND METHODS: From 2000 to 2002, the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid profiles in 1,416 individuals aged 19-56 years with no history of CHD: 652 type 1 diabetic patients (46% men, mean age 37 +/- 9 years) and 764 nondiabetic control subjects (50% men, mean age 39 +/- 9 years). These data combined with patient questionnaire results were used to determine prevalence of dyslipidemia and adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined using National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Type 1 diabetic subjects had significantly less dyslipidemia than nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic subjects and 15% of nondiabetic participants (P < 0.01). CONCLUSIONS: Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and undertreated in high-risk populations, such as patients with type 1 diabetes.     

Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes.

OBJECTIVE: To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics. RESEARCH DESIGN AND METHODS: The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined. RESULTS: Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 U.kg-1.day-1, P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 microU/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis. CONCLUSIONS: Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible.     

Carbohydrate-induced memory impairment in adults with type 2 diabetes

OBJECTIVE: Memory impairment is observed in adults with type 2 diabetes. The focus of this study was to determine whether acute carbohydrate consumption contributes to or exacerbates memory dysfunction. RESEARCH DESIGN AND METHODS: The impact of consuming 50 g of rapidly absorbed carbohydrate (one half bagel and white grape juice) at breakfast was examined in 19 adults with type 2 diabetes. Subjects (mean age 63 +/- 9 years, mean BMI 26.1 +/- 4.5 kg/m(2)) were tested, under fed and fasted conditions, on verbal declarative memory using both word list and paragraph recall tests (immediate and delayed [7-min] recall), Trails Test Part B as a measure of general brain function, and mood (subjectively monitoring global vigor and affect). RESULTS: Under baseline (fasting) conditions, elevated blood HbA(1c) was negatively associated with immediate and delayed paragraph recall performance (R(2) = 0.30; P = 0.024) and higher fasting blood glucose trended toward poorer word list recall (R(2) = 0.09; P = 0.102). Carbohydrate ingestion influenced measures of delayed, but not immediate, recall in a time-dependent fashion (time x food) (word list, P = 0.046; paragraph, P = 0.044) such that delayed recall was improved at 15 min postingestion but was impaired at 30 min. Neither Trails Test scores (P = 0.17) nor mood (affect, P = 0.68 and vigor, P = 0.45) were influenced by food ingestion. CONCLUSIONS: In adults with type 2 diabetes, poorer glycemic control is associated with lower performance on tests of declarative memory. Acute ingestion of high glycemic index carbohydrate foods further contributes to the underlying memory impairment.     

Emerging epidemic of type 2 diabetes in youth.

This review considers the epidemiologic evidence of an increasing incidence of type 2 diabetes in youth, the classification and diagnostic issues related to diabetes in young populations, pathophysiologic mechanisms relevant to the increasing incidence, the role of genetics and environment, and the community challenge for prevention and treatment. Type 2 diabetes in youth has been recognized to be frequent in populations of native North Americans and to comprise some 30 percent of new cases of diabetes in the 2nd decade of life, largely accounted for by minority populations and associated with obesity. Among Japanese schoolchildren, type 2 diabetes is seven times more common than type 1, and its incidence has increased more than 30-fold over the past 20 years, concomitant with changing food patterns and increasing obesity rates. The forms of diabetes seen in children and youth include typical type 1, occurring in all races; type 2, seen predominantly in minority youth; atypical diabetes, seen as an autosomal dominantly transmitted disorder in African-American populations; and maturity-onset diabetes of the young (MODY), seen rarely and only in Caucasians. Of the nonautoimmune forms of diabetes seen in youth, only type 2 diabetes is increasing in incidence. Proper classification requires consideration of onset (acute/severe versus insidious), ethnicity, family history, presence of obesity, and if necessary, studies of diabetes related autoimmunity. Insulin resistance predicts the development of diabetes in Pima Indians, in offspring of parents with type 2 diabetes, and in other high-risk populations. African-American children and youth have greater insulin responses during glucose tolerance testing and during hyperglycemic clamp study than do whites. There is also evidence of altered beta-cell function preceding the development of hyperglycemia. Of particular interest is the evidence that abnormal fetal and infantile nutrition is associated with the development of type 2 diabetes in adulthood. The thrifty phenotype hypothesis states that poor nutrition in fetal and infant life is detrimental to the development and function of the beta-cells and insulin sensitive tissues, leading to insulin resistance under the stress of obesity. The thrifty genotype hypothesis proposes that defective insulin action in utero results in decreased fetal growth as a conservation mechanism, but at the cost of obesity-induced diabetes in later childhood or adulthood. The vast majority of type 2 diabetes in adults is polygenic and associated with obesity. Monogenic forms (MODY, maternally transmitted mitochondrial mutations) are rare, but are more likely to appear in childhood. Linkage studies of the common polygenic type 2 diabetes have emphasized the heterogeneity of the disorder. The prevention and treatment of type 2 diabetes in children and youth is a daunting challenge because of the enormous behavioral influence, difficulty in reversing obesity, and typical nonadherence in this age-group. The emerging epidemic of type 2 diabetes in the pediatric population, especially among minorities whose proportion in the U.S. population is increasing, presents a serious public health problem. The full effect of this epidemic will be felt as these children become adults and develop the long-term complications of diabetes.     

Management of hypoglycemia in older adults with type 2 diabetes

Treatment of older adults with type 2 diabetes (T2D) is complex because they represent a heterogeneous group with a broad range of comorbidities, functional abilities, socioeconomic status, and life expectancy. Older adults with T2D are at high risk of recurring hypoglycemia, a condition associated with marked morbidity and mortality, because their counter-regulatory mechanism to hypoglycemia is attenuated, and recurring hypoglycemic episodes can lead to hypoglycemia unawareness. In addition, polypharmacy, a result of multiple chronic comorbidities (including heart disease, stroke, and chronic kidney disease), can increase the risk of severe hypoglycemia, especially when patients are taking sulfonylureas or insulin. Often the signs of hypoglycemia are nonspecific (sweating, dizziness, confusion, visual disturbances) and are mistaken for neurological symptoms or dementia. Consequences of hypoglycemia include acute and long-term cognitive changes, cardiac arrhythmia and myocardial infarction, serious falls, frailty, and death, often resulting in hospitalization, which come at a high economic cost. The American Diabetes Association has recently added three new recommendations regarding hypoglycemia in the elderly, highlighting individualized pharmacotherapy with glucose-lowering agents with a low risk of hypoglycemia and proven cardiovascular safety, avoidance of overtreatment, and simplifying treatment regimens while maintaining HbA1c targets. Thus, glycemic goals can be relaxed in the older population as part of individualized care, and physicians must make treatment decisions that best serve their patients’ circumstances. This article highlights the issues faced by older people with T2D, the risk factors for hypoglycemia in this population, and the challenges faced by health care providers regarding glycemic management in this patient group.