Prevalence and Predictors of Overweight and Insulin Resistance in Offspring of Mothers With Gestational Diabetes Mellitus

OBJECTIVE

Gestational diabetes mellitus (GDM) is associated with high birth weight in the offspring. This may lead to overweight and insulin resistance during childhood. The aim of the study was to assess the impact of GDM on overweight risk and insulin resistance in offspring.

RESEARCH DESIGN AND METHODS

BMI measurements were collected at age 2, 8, and 11 years from 232 offspring of mothers with GDM (OGDM) and compared with those from 757 offspring of mothers with type 1 diabetes (OT1D) and 431 offspring of nondiabetic mothers (ONDM) born between 1989 and 2000. Insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) was determined at age 8 and 11 years in 751 children (74 OGDM). Overweight was defined as BMI percentile ≥90; insulin resistance was defined by HOMA-IR.

RESULTS

Overweight prevalence was increased in OGDM compared with OT1D and to ONDM throughout childhood (age 11 years 31.1, 15.8, and 15.5%; P = 0.005). Maternal obesity was an important predictor of overweight risk in children (age 11 years odds ratio 7.0 [95% CI 1.8–27.7]; P = 0.006); birth size and maternal smoking during pregnancy were inconsistently associated with and treatment of GDM during pregnancy did not affect overweight risk. HOMA-IR was increased in OGDM compared with offspring of ONDM mothers (P = 0.01, adjusted for sex and age) and was associated with the child''s BMI (P = 0.004).

CONCLUSIONS

Overweight and insulin resistance in children is increased in OGDM compared with OT1D or ONDM. The finding that overweight risk is associated mainly with maternal obesity suggests that familial predisposition contributes to childhood growth in these offspring.The increasing prevalence of obesity in children is a major burden not only for affected individuals but also for the health economy. To develop preventive strategies, it is useful to identify subjects at high risk and factors that predict overweight risk. It is widely accepted that gestational and perinatal factors influence weight development in childhood, and several studies indicated that intrauterine exposure to maternal diabetes conveys high risk for obesity and type 2 diabetes in offspring of mothers with diabetes regardless of maternal diabetes type (1–3). Furthermore, an association between increasing hyperglycemia in pregnancy and increasing risk of childhood obesity has been reported (4). The findings have led to the hypothesis that fetal overnutrition leads to increased risk of obesity and insulin resistance later in life (5).Not all studies, however, show a direct relationship between childhood obesity and diabetes. Our own studies show that maternal type 1 diabetes is unlikely to be a primary association with obesity in offspring, but that factors such as high birth size predispose offspring of mothers with type 1 diabetes (OT1D) to overweight during childhood (6). In addition, others report that maternal pregravid BMI is the strongest predictor of childhood obesity independent of maternal glucose status or birth weight (7). The aim of our study was to determine whether maternal diabetes per se is a risk factor for childhood obesity and insulin resistance by comparing outcome in offspring of mothers with gestational diabetes mellitus (OGDM) and OT1D. Because a previous study reported age-dependent associations of gestational diabetes mellitus (GDM) with higher child weight status (1), a secondary objective was to examine whether associations between offspring weight and peri- or postnatal factors are consistent over time.     

Risk Factors for Childhood Overweight in Offspring of Type 1 Diabetic Women With Adequate Glycemic Control During Pregnancy: Nationwide follow-up study in the Netherlands

OBJECTIVE

Pregnancy in type 1 diabetic women remains a high-risk situation for both mother and child. In this study, we investigated long-term effects on body composition, prevalence of overweight, and insulin resistance in children of type 1 diabetic women who had had adequate glycemic control during pregnancy (mean A1C 6.2%), and we related their outcome to perinatal factors, including macrosomia (birth weight >90th percentile).

RESEARCH DESIGN AND METHODS

Anthropometric measurements were performed at 6–8 years of age in 213 offspring of type 1 diabetic mothers who participated in a previous nationwide study. Homeostasis model assessment of insulin resistance (HOMA-IR) was determined from a fasting blood sample in 155 of these children. In addition, we studied BMI standard deviation score (SDS) growth trajectories. Results were compared with national reference data.

RESULTS

The prevalence of overweight in the study population was not different from that in the reference population. However, children who were born macrosomic showed twice as much overweight as nonmacrosomic children. Macrosomia and maternal overweight were independent predictors of childhood overweight. Overweight children showed an increase in BMI SDS starting already after 6 months of age and had a significantly increased HOMA-IR.

CONCLUSIONS

In type 1 diabetic women with adequate glycemic control during pregnancy, long-term effects on body composition and overweight in their offspring at school age are limited and related mainly to macrosomia at birth. Possible targets for prevention of childhood overweight are fetal macrosomia, maternal overweight, and an increase in BMI SDS during the first years of life.Perinatal outcome in diabetic pregnancies has improved dramatically over the past decades, mainly due to improvements in maternal glycemic control and in obstetric and neonatal care (1). However, despite these improvements, pregnancy in women with type 1 diabetes remains a high-risk situation for both mother and child as we have shown in a Dutch nationwide prospective study (2). The incidence of maternal and neonatal complications such as congenital malformations (9%) and macrosomia (45%) was still high despite good prepregnancy care and overall adequate glycemic control during pregnancy (mean A1C 6.2%). Similar rates of complications have been found in Denmark (3) and in the U.K. (4) and have also been found in type 2 diabetic pregnancies (4–6). Evidence is accumulating that an altered intrauterine environment has long-term effects on the offspring''s development. Previous studies have shown the effects of a diabetic pregnancy on several aspects of development in the offspring such as body composition and glucose homeostasis (see ref. 7 for an overview). However, most studies included small or mixed study cohorts concerning offspring of women with pregestational type 1 and type 2 diabetes as well as gestational diabetes mellitus. Furthermore, most studies considered offspring within a wide range of ages or those born >20 years ago when glycemic control was not as good as in current times. Therefore, we conducted a follow-up study in our nationwide Dutch cohort of type 1 diabetic women to investigate the long-term effects of current (adequate) control and treatment during pregnancy on body composition, childhood overweight, and BMI growth trajectories in their offspring at school age. Furthermore, we related these outcomes to perinatal factors, including macrosomia at birth, and investigated insulin resistance to determine whether possible effects on body composition would have metabolic consequences already at this young age.     

Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

OBJECTIVE

Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring.

RESULTS

All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring''s ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring''s logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P = 0.03) persisted even after adjustment for the offspring''s ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05).

CONCLUSIONS

In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk.Microalbuminuria remains the best predictive marker for the development of overt diabetic nephropathy and represents an independent risk factor for cardiovascular disease (CVD) (1). Evidence indicating that the risk for the development of microalbuminuria and diabetic nephropathy is partly genetic and may relate to the inheritance of genes associated with CVD is accumulating (2). Several studies have shown familial aggregation of renal disease in type 1 diabetes (2,3), and a family history of hypertension, dyslipidemia, insulin resistance, type 2 diabetes, or a cluster of these cardiovascular risk factors has been associated with an increased risk of diabetic nephropathy (2,4).In particular, several lines of evidence have highlighted the fact that predisposition to hypertension might be a risk factor for the development and progression of diabetic nephropathy in individuals with type 1 diabetes (4–8), and, therefore, the inheritance of blood pressure–related genes might also contribute to abnormal albumin excretion and renal damage. Parental hypertension has been associated with changes in renal hemodynamics (9) and with the development of diabetic nephropathy in the offspring with diabetes (5–8). However, the relationship between family history of hypertension and albuminuria has not been confirmed in all studies (10) and in the majority of studies, confirmation has been based on a single blood pressure assessment in the parents (7,8) or on a questionnaire-based history of parental hypertension. In addition, the effect of parental blood pressure, as was that of other heritable factors, has been mainly investigated in adults with diabetes, whereas it has been seldom studied in children and adolescents (11,12).Understanding the role of such a familial/genetic effect of blood pressure on renal disease would be particularly important in adolescents with type 1 diabetes, who represent a vulnerable group at risk of vascular complications (13). In particular, the identification of familial/genetic factors predisposing to diabetic nephropathy and the understanding of their interplay with glycemic control and the hormonal and metabolic changes of puberty could help in identifying subjects at higher risk for diabetes complications, who therefore require more intensive treatment to prevent them. The aim of the present study was to assess whether parental ambulatory blood pressure (ABP) was related to variations in the same trait and in albumin excretion rates in young offspring with childhood-onset type 1 diabetes.     

Personality Traits as Predictors of Adherence in Adolescents With Type I Diabetes

TOPIC: Diabetes is a serious, chronic illness with long‐term implications for health and lifestyle. Significant differences in health outcome may be achieved as a result of the degree of adherence to recommended diabetes management regimens. Adherence is a particularly challenging issue with adolescents with diabetes. PURPOSE: The present study examined the association between primary personality traits and adolescent adherence to prescribed diabetes management regimens. SOURCES: A measure of the five‐factor model of personality was administered to a sample of adolescents with insulin‐dependent diabetes mellitus. Five self‐reported indicators of adherence were assessed: blood glucose monitoring, insulin administration, diet, exercise, and most recent glycosylated hemoglobin (HbA1c) level. CONCLUSIONS: Results revealed a pattern of significant correlations between the Conscientiousness and Neuroticism personality domains and one or more self‐reported adherence behaviors. In addition, correlations were also found between one facet of Extraversion and one facet of Agreeableness. These suggestive results, if replicated in larger studies, provide useful information to clinicians as they design and monitor individualized diabetes management regimens for adolescents.     

Relationship Between Overweight and Obesity With Hospitalization for Heart Failure in 20,985 Patients With Type 1 Diabetes: A population-based study from the Swedish National Diabetes Registry

OBJECTIVE

To investigate the potential relationship between overweight, obesity, and severe obesity and the risk of hospitalization for heart failure (HF) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied patients with type 1 diabetes included in the Swedish National Diabetes Registry during 1998–2003, and they were followed up until hospitalization for HF, death, or 31 December 2009. Cox regression was used to estimate relative risks.

RESULTS

In a sample of 20,985 type 1 diabetic patients (mean age, 38.6 years; mean BMI, 25.0 kg/m²), 635 patients were hospitalized with HF as a primary or secondary diagnosis during a median follow-up of 9.1 years. Cox regression adjusting for age, sex, diabetes duration, smoking, HbA_1c, systolic and diastolic blood pressures, and baseline and intercurrent comorbidities (including myocardial infarction) showed a significant relationship between BMI and hospitalization for HF (P < 0.0001). In reference to patients in the BMI 20–25 kg/m² category, hazard ratios (HRs) were as follows: HR 1.22 (95% CI, 0.83–1.78) for BMI <20 kg/m²; HR 0.94 (95% CI, 0.78–1.12) for BMI 25–30 kg/m²; HR 1.55 (95% CI, 1.20–1.99) for BMI 30–35 kg/m²; and HR 2.90 (95% CI, 1.92–4.37) for BMI ≥35 kg/m².

CONCLUSIONS

Obesity, particularly severe obesity, is strongly associated with hospitalization for HF in patients with type 1 diabetes, whereas no similar relation was present in overweight and low body weight.Heart failure (HF) is a growing public health issue, and it was recently estimated that nearly 6 million Americans older than age 20 had a clinical diagnosis of HF (1). By 2030, an additional 3 million people in the United States are predicted to have HF, a 25% increase in prevalence from 2010 (1). HF also is associated with poor prognosis, with an age-adjusted 5-year mortality rate of 50% after onset (2,3) even in the setting of modern treatment (4). Patients with symptomatic HF have a significant impact on health care spending in industrialized countries (5,6). Consequently, identifying risk factors and striving to prevent clinical HF through treatment should be a high priority, as should early identification of preclinical HF in high-risk populations, such as patients with diabetes.Patients with type 1 diabetes have been shown to be at particularly high risk for HF. Recent work from our group demonstrated that not only poor diabetes control but also BMI was independently associated with increased risk of HF, but the nature of the association between BMI and hospitalization for HF was not explored (7).Obesity also has been shown to be an important risk factor for HF in the general population (8), and in several studies obesity has shown a graded increase in risk across BMI categories (9,10). In this study, we examined whether an association exists between overweight or modest obesity and major increases in risk of HF, or if these risks primarily are limited to more severe stages of obesity.     

Emotional Regulation and Diabetes Distress in Adults With Type 1 and Type 2 Diabetes

OBJECTIVETo explore the correlates of diabetes-related distress (DD) with psychometrically valid assessments of emotional regulation in individuals with type 1 and type 2 diabetes.RESEARCH DESIGN AND METHODSAdults with diabetes (n = 298) were assessed for psychological issues possibly associated with diabetes and were further evaluated with measures of negative emotional experience (ER-Exp) and skill at regulating such experiences (ER-Skill) and measures of DD, perceived psychosocial stress, diabetes literacy, and diabetes self-care.RESULTSER-Exp was directly related to DD, while ER-Skill was inversely related to DD. Together, these ER variables displayed a medium-size relationship (β = 0.45) with DD. Inclusion of variables related to diabetes self-care and perceived psychosocial stress was associated with only an 18% reduction (i.e., β = 0.45 to β = 0.38) in the strength of this relationship, while the magnitude of relationships between DD and perceived psychosocial stress (β = 0.15) and diabetes self-care (β = −0.09) was relatively small.CONCLUSIONSThese data suggest that DD is meaningfully linked with negative emotionality, and skill at regulating such emotions, in adults with diabetes. This relationship appears to be stronger than that between DD and perceived psychological stress or diabetes self-care. If so, DD (and possibly A1C) may be improved in those with diabetes and difficulties with negative emotionality.     

Promoting Normalization in Families With Preschool Children With Type 1 Diabetes

issues and purpose. The family environment is the most important influence on child adaptation to type 1 diabetes. A plan of care assists parental adaptation in families with a preschool child with type 1 diabetes.
conclusions. The family environment is affected by the family's progress toward normalcy. Normalization can be facilitated by nursing interventions that promote parental mutuality in management and the development of a parental support system.
practice implications. Nurses can provide education about Type 1 diabetes and its management in preschool children to fathers, other family members, and family friends to encourage their involvement in caregiving. Parental mutuality in management and an adequate parental instrumental support system facilitates normalization and affects the family environment, thus promoting child adaptation.     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.     

Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes

OBJECTIVEInsulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSPubertal youth (n = 284) aged 12–21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO₂peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear.RESULTSIn adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO₂peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D.CONCLUSIONSObesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.     

Neck Circumference Positively Related With Central Obesity, Overweight, and Metabolic Syndrome in Chinese Subjects With Type 2 Diabetes: Beijing Community Diabetes Study 4

OBJECTIVE

To investigate the association between neck circumference and central obesity, overweight, and metabolic syndrome in Chinese individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 3,182 diabetic subjects (aged 20–80 years) were recruited from 15 community health centers in Beijing using a multistage random sampling approach.

RESULTS

Receiver operating characteristic analysis showed that the area under the curve for neck circumference and central obesity was 0.77 for men and 0.75 for women (P < 0.001). Furthermore, a neck circumference of ≥38 cm for men and ≥35 cm for women was the best cutoff point for determining overweight subjects. A neck circumference of ≥39 cm for men and ≥35 cm for women was the best cutoff point to determine subjects with metabolic syndrome.

CONCLUSIONS

In the present study, neck circumference is positively related with BMI, waist circumference, and metabolic syndrome in Chinese individuals with type 2 diabetes.Neck circumference (NC) as an index for upper-body subcutaneous adipose tissue distribution has been evaluated in relation to cardiovascular risk factors, insulin resistance, and biochemical components of metabolic syndrome (MS) (1–4). However, epidemiological population-based studies on the clinical significance of NC in connection with overweight and MS in diabetic people are lacking. The aim of this study was to determine whether NC alone can predict overweight and central obesity and to evaluate the association between NC and MS.     

Smoking Is Associated With Reduced Risk of Autoimmune Diabetes in Adults Contrasting With Increased Risk in Overweight Men With Type 2 Diabetes: A 22-year follow-up of the HUNT study

OBJECTIVE

To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes.

RESEARCH DESIGN AND METHODS

We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984–2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models.

RESULTS

The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30–0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18–0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10–1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23–0.57).

CONCLUSIONS

In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.Data on the influence of smoking on autoimmune diabetes are limited. A protective effect seems plausible because an anti-inflammatory effect of nicotine has been demonstrated both in vitro (1) and in vivo (2). Also, an inhibitory effect of nicotine on autoimmune diabetes has been documented in one animal study (3). In a previous study based on prospective data from the Norwegian Nord-Trøndelag Health Study (HUNT) 1984–1997, we found a reduced risk of latent autoimmune diabetes in adults (LADA) in smokers (4). Confirmatory and extended evidence for such an effect is, however, desirable.In contrast, smoking, in particular heavy smoking, is clearly associated with an increased risk of type 2 diabetes (5). The increased risk has been attributed to impaired insulin sensitivity (6), increased systematic inflammation (7), greater accumulation of abdominal adipose tissue (8), and/or adverse effects on pancreatic tissue and β-cell function (9). Overweight may modify the influence of smoking on type 2 diabetes; in one Japanese study, the association between smoking and type 2 diabetes was limited to overweight individuals (10), and findings from a Finnish study suggest that smoking is more detrimental in individuals with high BMI (11). Further studies on a possible interaction are, however, needed.The aim of this study was to extend our previous analyses of smoking in autoimmune diabetes in adults with regard to cases and follow-up time and also to include in-depth analysis of the established association of smoking with type 2 diabetes.     

Serum Monocyte Chemoattractant Protein-1 Concentrations Associate With Diabetes Status but Not Arterial Stiffness in Children With Type 1 Diabetes

OBJECTIVE

The relationship between circulating markers of inflammation and arterial stiffness in children with type 1 diabetes is not well studied. We tested whether inflammatory monocyte chemoattractant protein (MCP)-1 concentrations correlate with arterial stiffness or type 1 diabetes status.

RESEARCH DESIGN AND METHODS

MCP-1 concentrations and radial tonometry data were available for 98 children with type 1 diabetes and 55 healthy control subjects. Arterial stiffness was calculated as augmentation index corrected for a heart rate of 75 (AI75). Correlation between MCP-1 and AI75 and differences in MCP-1 concentrations between case and control subjects were tested.

RESULTS

MCP-1 was significantly higher in children with type 1 diabetes than in control subjects (P < 0.001). However, there were no correlations between MCP-1 and AI75 in the overall sample or upon stratification by type 1 diabetes status (range P = 0.28–0.66).

CONCLUSIONS

Circulating MCP-1 was not associated with arterial stiffness but was significantly elevated in children with type 1 diabetes, indicating a proinflammatory state in children as young as 10 years. The clinical significance of MCP-1 elevation in type 1 diabetes needs further investigation.Type 1 diabetes is associated with endothelial inflammation and arterial stiffness. We previously demonstrated that arterial stiffness is apparent in type 1 diabetic children as young as 10 years when compared with matched control subjects (1) but noted poor correlation with both traditional cardiovascular disease (CVD) risk factors (A1C, LDL cholesterol, and family history) and novel serum CVD risk factors (interleukin-6, tumor necrosis factor, C-reactive protein, superoxide dismutase, and nitric oxide) (1,2). Notably, a genetic association with arterial stiffness was seen (3). We postulated that the lack of correlation between arterial stiffness and previously studied risk factors was likely representative of the low short-term absolute risk for macrovascular events in our young type 1 diabetic cohort. Given that the majority of CVD events in type 1 diabetic patients are clustered among those with concurrent diabetic nephropathy, we sought to determine if monocyte chemoattractant protein (MCP)-1, a serum marker with known correlation to CVD events and diabetic nephropathy, would correlate with arterial stiffness in children with type 1 diabetes (4). As MCP-1 is stimulated by chronic hyperglycemia and is responsible for induction of superoxide anion, cytokine production, and adhesion molecule expression (5), exploration of potential correlation with global vascular dysfunction in children with type 1 diabetes was warranted. In this analysis, we sought to determine whether MCP-1 concentrations correlate with arterial stiffness as measured by radial artery tonometry and to validate previous associations between circulating MCP-1 concentrations and type 1 diabetes status in a case-control analysis.     

Prevalence of Morphometric Vertebral Fractures in Patients With Type 1 Diabetes

OBJECTIVE

Several studies showed low bone mineral density (BMD) and elevated risk of symptomatic fractures in patients with type 1 diabetes (T1D). To our knowledge, there has been no investigation on the prevalence of asymptomatic vertebral fractures (VFx) in T1D. In the current study, we assessed BMD and the prevalence of VFx in T1D.

RESEARCH DESIGN AND METHODS

We evaluated 82 T1D patients (26 males and 56 females, aged 31.1 ± 8.6 years, BMI 23.5 ± 3.3 kg/m², disease duration 12.8 ± 8.3 years) and 82 controls (22 females and 60 males, aged 32.9 ± 5.8 years, BMI 23.9 ± 4.8 kg/m²). Spinal and femoral BMD (as Z-score, Z-LS and Z-FN, respectively) and the prevalence of VFx were evaluated by dual X-ray absorptiometry.

RESULTS

T1D patients had lower Z-LS and Z-FN than controls (−0.55 ± 1.3 vs. 0.35 ± 1.0, P < 0.0001, and −0.64 ± 1.1 vs. 0.29 ± 0.9, P < 0.0001, respectively) and a higher prevalence of VFx (24.4 vs. 6.1%, P = 0.002). Age, diabetes duration, age at diabetes manifestation, glycosylated hemoglobin, Z-LS, Z-FN, and the prevalence of chronic complications were similar for patients with and without VFx. In the logistic regression analysis, the presence of VFx was associated with the presence of T1D but not with lumbar spine BMD. Whereas moderate or severe VFx was associated with low lumbar spine BMD in the whole combined group of T1D patients and controls, there was no association between moderate or severe VFx and lumbar spine BMD in the T1D group.

CONCLUSIONS

T1D patients have low BMD and elevated prevalence of asymptomatic VFx, which is associated with the presence of T1D independently of BMD.Type 1 diabetes (T1D) has been suggested to be associated with an increased risk of fractures (1). The exact mechanisms accounting for bone fragility in T1D are not known in detail (2,3). In most but not all studies, bone mineral density (BMD), as measured by dual X-ray absorbtiometry (DXA), appears to be reduced (1–3). In particular, in adults, who have reached the peak of bone mass, the findings are somewhat heterogeneous, although most studies point toward a negative effect of T1D on BMD (2,4). In keeping with this, combined study analysis estimated that T1D increases the risk of clinical fractures by 1- to 2-fold at the spine, 1.5- to 2.5-fold at the hip, and 2-fold at the distal radius (2). No data are available regarding the risk of asymptomatic morphometric vertebral fracture (VFx) in T1D patients. This is an important lack of knowledge, because it is known that the presence of a morphometric VFx increases the risk of a subsequent spinal or hip fracture, regardless of BMD (5). In addition, a recent meta-analysis demonstrated an absolute risk of hip fracture in T1D higher than that expected on the basis of BMD variation (1). This suggests that in T1D the reduction of BMD estimates the fracture risk only partially. In this study, we evaluated the BMD and the prevalence of morphometric VFx in a group of adult T1D patients.     

Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE

Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Eight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.

RESULTS

Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.

CONCLUSIONS

Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.Cognitive abilities are essential for independent living in later life, and some domains of cognitive functioning decline in mean level from relatively early adulthood (1). Age-related cognitive decline is accompanied by pathological changes in the brain, including cerebral microvascular changes, and although individual differences exist in the severity of age-related microvascular damage in the brain, this is difficult to investigate noninvasively. Systemic atherosclerotic changes in the body may serve as a marker of vascular-related changes in the brain (2) that, in turn, lead to cognitive deficits (3,4). However, the potential of large vessel changes distant from the brain itself to function as markers of cognitive decline remains unclear. We aimed to study a range of measures of clinical and subclinical macrovascular disease that focus on different areas of the vasculature or different underlying pathophysiological mechanisms to assess which of these might function as proxies of cognitive decline.Understanding the role of macrovascular disease in age-related cognitive impairment is particularly important in diabetes, given the higher prevalence of atherosclerotic large vessel disease as well as the accelerated cognitive decline and increased risk of cognitive impairment (5,6) associated with this condition, and the potentially modifiable nature of macrovascular disease (7). The prevalence of stroke, of transient ischemic attack (TIA) (8), and of coronary heart disease (9) are higher in diabetic populations than in nondiabetic populations, and average natriuretic peptide levels, a marker of cardiac stress, are increased (10). Markers of subclinical atherosclerosis also are altered, with increased average carotid intima-media thickness (cIMT) (11) and reduced mean ankle brachial index (ABI) (12). Despite this, investigation into the role of macrovascular disease in age-related cognitive impairment in people with diabetes is limited compared with investigation into this issue in the general (predominantly nondiabetic) population. We set out to determine the association of a variety of measures of subclinical macrovascular disease and cardiovascular event categories with cognitive decline in a sample of older people, all of whom had diabetes (the Edinburgh Type 2 Diabetes Study [ET2DS]). We did so using two cognitive outcomes, actual late-life cognitive change over a 4-year period and estimated lifetime cognitive change. These analyses are timely given the increasing prevalence of diabetes at younger ages (13) that, together with greater survival (14) and greater lifetime exposure to diabetes in current generations, is likely to contribute to increasing prevalence of cognitive impairment.     

1型糖尿病儿童血、尿一氧化氮水平观察

目的:探讨儿童1型糖尿病(TlDM)患者血尿一氧化氮水平及意义。方法:采用镉柱层析还原法,测定107例TlDM患儿(年龄10.5±2.4岁)尿硝酸盐(NO_3~-)含量(男性49例,女性58例),同时测定44例患儿血NO_3~-(男性24例,女性20例)及30例健康儿童(10.1±1.8岁)血、尿NO_3~-。结果:TlDM组与对照组血NO_3~-无显著差异(TlDM组55±49μmol/L,对照组76±26μmol/L,P>0.05),但尿NO_3~-量有显著差异。且TlDM组各病程段均高于对照组(527±234μmol/L,P<0.001)。结论:儿童TlDM患者尿NO_3~-排泄量显著增加,并随着尿糖的转阴及病程的延长而减低,增高的尿NO_3~-可能与高血糖所致的DM早期肾脏高灌注、高滤过有重要相关性,并可能参与糖尿病肾病的发生。