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Articles by R. J. Heine
Total Records ( 5 ) for R. J. Heine
  A. W. Van Deutekom , R. J. Heine and S. Simsek
  Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD)-compared with single and low-titre autoantibody-is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups.
  M. C. Adriaanse , J. M. Dekker , R. J. Heine , F. J. Snoek , A. J. Beekman , C. D. Stehouwer , L. M. Bouter , G. Nijpels and F. Pouwer
  Objective  To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2).

Research design and methods  Cross-sectional data from a population-based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score ≥ 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels.

Results  The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P < 0.01), respectively. Depression was significantly more common in women with IGM [odds ratio (OR) = 3.60, 95% confidence interval (CI) = 1.57 to 8.28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non-significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms reduced the strength of these associations.

Conclusions  Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could be intermediate factors.

  F. J. Snoek , N. C. W. Van Der Ven , J. W. R. Twisk , M. H. E. Hogenelst , A. M. E. Tromp-Wever , H. M. Van Der Ploeg and R. J. Heine
  Objective  To test the effectiveness at 6 and 12 months' follow-up of group cognitive behavioural therapy (CBT) compared with blood glucose awareness training (BGAT) in poorly controlled Type 1 diabetic patients and to explore the moderating effect of baseline depression.

Research design and methods  Adults with Type 1 diabetes (n = 86) with glycated haemoglobin (HbA1c) ≥ 8% were randomized to CBT or BGAT. Primary outcome was HbA1c control. Secondary outcomes were: self-care, diabetes-related distress (Problem Areas in Diabetes scale; PAID), diabetes self-efficacy (Confidence in Diabetes Self-care scale; CIDS) and depressive symptoms (Centre for Epidemiological Studies - Depression scale; CES-D). Measurements were scheduled before CBT and BGAT, and at 3, 6 and 12 months after. Differential effects were analysed for the subgroup of patients reporting low vs. high baseline levels of depression.

Results  Neither CBT nor BGAT had a significant impact on HbA1c at 6 and 12 months' follow-up. Both interventions resulted in lower depressive symptoms (CES-D 15.7-13.3, P = 0.01) up to 12 months, but only CBT was effective in lowering HbA1c in patients with high baseline depression scores (HbA1c 9.5-8.8%) up to 1 year of follow-up (P = 0.03).

Conclusions  Our findings suggest that group CBT can effectively help Type 1 diabetic patients with co-morbid depression achieve and maintain better glycaemic outcomes.

  S. Sarwat , L. L. Ilag , M. A. Carey , D. S. Shrom and R. J. Heine
  Aims  Self-monitoring of blood glucose (SMBG) is an important self-management tool for insulin-treated patients with Type 2 diabetes mellitus (T2DM). Its value in estimating glycaemic control in insulin-treated T2DM patients remains unclear. The relationship between glycated haemoglobin (HbA1c) and SMBG measures in T2DM patients treated with premixed insulin lispro mixtures or basal insulin glargine was examined.

Methods  HbA1c and plasma equivalent glucose (PGe) data derived from SMBG profiles were pooled from five randomized clinical trials of patients with T2DM on one or more oral glucose-lowering medication ± 0-2 insulin injections per day switching to insulin lispro mixtures (N = 317) or glargine (N = 306). Patients generated seven-point SMBG profiles three times in a 2-week period prior to each HbA1c measurement. Pearson's correlation coefficients (r) were calculated for PGe values and HbA1c. Receiver-operating characteristic (ROC) curves determined the ability of sets of PGe to estimate HbA1c (< or > 7.0%).

Results  Mean ± standard deviation age was 57.5 ± 9.5 years, body mass index 31.3 ± 5.6 kg/m2, 52.5% were male and HbA1c overall was 7.4 ± 1.0% at end-point. Among individual SMBG measures, r for HbA1c ranged from 0.34 to 0.49. For means of two or more PGe measures, r for HbA1c ranged from 0.51 to 0.59. Correlations were similar for either regimen. ROC curves were consistent with the correlation data.

Conclusions  These data provide patients and clinicians information on the relationship between HbA1c and SMBG measurements in patients with T2DM, and support the value of frequent blood glucose measurements for assessing overall glycaemic control.

  B. Guigas , J. E. de Leeuw van Weenen , N. van Leeuwen , A. M. Simonis-Bik , T. W. van Haeften , G. Nijpels , J. J. Houwing-Duistermaat , M. Beekman , J. Deelen , L. M. Havekes , B. W. J. H. Penninx , N. Vogelzangs , E. van t Riet , A. Dehghan , A. Hofman , J. C. Witteman , A. G. Uitterlinden , N. Grarup , T. Jorgensen , D. R. Witte , T. Lauritzen , T. Hansen , O. Pedersen , J. Hottenga , J. A. Romijn , M. Diamant , M. H. H. Kramer , R. J. Heine , G. Willemsen , J. M. Dekker , E. M. Eekhoff , H. Pijl , E. J. de Geus , P. E. Slagboom and L. M. t Hart


Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans.


Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis.


rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (= 5.5*10−4) but again not in men (= 0.34).


The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene.

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