Rectal sensitivity correlated with gastrointestinal-mediated glucose disposal, but not the incretin effect.

OBJECTIVE: The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. DESIGN AND METHODS: For a cross-sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). RESULTS: Sixty-five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = -0.204, p = .106), but an association was found with GIGD (rho -0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. CONCLUSIONS: Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. PREVIOUSLY PUBLISHED: Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658-P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658-P. https://doi.org/10.2337/db23-1658-P.

Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy.

CONTEXT: Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing. OBJECTIVE: This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life. METHODS: A retrospective follow-up was conducted of GD patients that participated in a randomized trial from 1997 to 2001. Demographic and clinical data were obtained from medical records and questionnaires. Biobank samples were analyzed for inflammatory biomarkers and compared with age- and sex-matched healthy individuals. RESULTS: We included 83% (182/218) of the patients from the original study. At the end of follow-up, normal thyroid function was achieved in 34%. The remaining had either active disease (1%), spontaneous hypothyroidism (13%), or had undergone ablative treatment with radioiodine (40%) or thyroidectomy (13%). Age younger than or equal to 40 years, thyroid eye disease (TED), smoking, and elevated levels of interleukin 6 and tumor necrosis factor receptor superfamily member 9 (TNFRS9) increased the risk of relapsing disease (odds ratio 3.22; 2.26; 2.21; 1.99; 2.36). At the end of treatment, CD40 was lower in patients who maintained normal thyroid function (P = .04). At the end of follow-up, 47% had one or more autoimmune diseases, including vitamin B12 deficiency (26%) and rheumatoid arthritis (5%). GD patients who developed hypothyroidism had reduced quality of life. CONCLUSION: Careful lifelong monitoring is indicated to detect recurrence, hypothyroidism, and other autoimmune diseases. Long-term ATD treatment emerges as a beneficial first-line treatment option, especially in patients with young age at onset or presence of TED.

Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study.

OBJECTIVE: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood. DESIGN: Cross-sectional study. METHODS: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH. RESULTS: Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = -0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (-0.15 normalized protein expression [NPX], P = .0001, and -0.25 NPX, P = .0003, respectively). CONCLUSIONS: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

The Composite Autonomic Symptom Score 31 Questionnaire: A Sensitive Test to Detect Risk for Autonomic Neuropathy.

Background and Aims: Autonomic neuropathy is a common but often neglected complication of diabetes, prediabetes, and even in individuals with an elevated risk of diabetes. The Composite Autonomic Symptom Score (COMPASS) 31 is a validated and easy-to-use questionnaire regarding autonomic symptoms. We aimed to use a digitally, Norwegian version of the COMPASS 31 in people with different durations of diabetes and healthy controls to consider feasibility and to investigate if scores could discriminate between positive and negative outcomes for established tests for diabetic neuropathy, including cardiovascular autonomic neuropathy (CAN) and a novel method of examining the gastrointestinal visceral sensitivity. Method: We included 21 participants with longstanding type 2 diabetes, 15 with early type 2 diabetes, and 30 matched controls. The mean age for all groups was 69 years. Participants were phenotyped by cardiovascular autonomic reflex tests, electrical skin conductance, sural nerve electrophysiology, and the monofilament test. As a proxy for gastrointestinal visceral and autonomic nerve function, evoked potentials were measured following rapid rectal balloon distention. Results: Participants with longstanding diabetes scored a median (IQR) of 14.9 (10.8-28.7) points, early diabetes of 7.3 (1.6-15.2), and matched controls of 8.6 (4.1-21.6), p = 0.04. Women and men scored 14.4 (5.5-28.7) and 7.8 (3.6-14.6) points, respectively, p = 0.01. Participants with definite or borderline CAN scored 14.3 (10.4-31.9) points, compared to participants with no CAN, 8.3 (3.2-21.5), p = 0.04. Lowering the diagnostic cut-off from 16 to 10 points increased the sensitivity from 0.33 to 0.83, with a decreased specificity from 0.68 to 0.55. Conclusion: We successfully used COMPASS 31 in Norwegian. Thus, following the guidelines, we suggest clinical implementation for the assessment of autonomic neuropathy. Participants with longstanding diabetes had an increased likelihood of symptoms and signs of autonomic neuropathy. For screening purposes, the sensitivity was improved by lowering the cut-off to 10 points, with a lower score nearly excluding the diagnosis.

Intensified follow-up of patients with type 1 diabetes and poor glycaemic control: a multicentre quality improvement collaborative based on data from the Norwegian Diabetes Register for Adults.

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) and poor glycaemic control are at high risk of developing microvascular and macrovascular complications. The aim of this study was to determine if a quality improvement collaborative (QIC) initiated by the Norwegian Diabetes Register for adults (NDR-A) could reduce the proportion of patients with T1DM with poor glycaemic control (defined as glycated haemoglobin (HbA1c)≥75 mmol/mol) and reduce mean HbA1c at participating clinics compared with 14 control clinics. METHOD: Multicentre study with controlled before and after design. Representatives of 13 diabetes outpatient clinics (n=5145 patients with T1DM) in the intervention group attended four project meetings during an 18-month QIC. They were required to identify areas requiring improvement at their clinic and make action plans. Continuous feedback on HbA1c outcomes was provided by NDR-A during the project. In total 4084 patients with type 1 diabetes attended the control clinics. RESULTS: Between 2016 and 2019, the overall proportion of patients with T1DM and HbA1c≥75 mmol/mol in the intervention group were reduced from 19.3% to 14.1% (p<0.001). Corresponding proportions in the control group were reduced from 17.3% (2016) to 14.4% (2019) (p<0.001). Between 2016 and 2019, overall mean HbA1c decreased by 2.8 mmol/mol (p<0.001) at intervention clinics compared with 2.3 mmol/mol (p<0.001) at control clinics. After adjusting for the baseline differences in glycaemic control, there were no significant differences in the overall improvement in glycaemic control between intervention and control clinics. CONCLUSIONS: The registry linked QIC did not result in a significantly greater improvement in glycaemic control at intervention clinics compared with control clinics. However, there has been a sustained improvement in glycaemic control and importantly a significant reduction in the proportion of patients with poor glycaemic control at both intervention and control clinics during and after the QIC time frame. It is possible that some of this improvement may be due to a spillover effect from the QIC.

Plasma-Metanephrines in Patients with Autoimmune Addison's Disease with and without Residual Adrenocortical Function.

PURPOSE: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. METHODS: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). RESULTS: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. CONCLUSION: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.

Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison's Disease.

BACKGROUND: No reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison's disease (AAD), leading to overtreatment with alarming and persistent side effects or undertreatment, which could be fatal. OBJECTIVE: To explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD. METHODS: Step 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In 3 of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and 3, 4, and 6 hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD. RESULTS: Step 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and levels of ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression. CONCLUSIONS: We introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.

Residual Corticosteroid Production in Autoimmune Addison Disease.

CONTEXT: Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis. OBJECTIVE: To determine frequencies and clinical features of residual corticosteroid production in patients with AAD. DESIGN: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. RESULTS: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001). CONCLUSION: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.

Type 2 diabetes in general practice in Norway 2005-2014: moderate improvements in risk factor control but still major gaps in complication screening.

OBJECTIVE: To assess the status of type 2 diabetes care in general practice and changes in the quality of care between 2005 and 2014, and to identify areas of diabetes care requiring improvement. RESEARCH DESIGN AND METHODS: Two cross-sectional surveys were performed that included patients with type 2 diabetes in selected areas (n=9464 in 2014, n=5463 in 2005). Quality of care was assessed based on key recommendations in national guidelines. Differences in clinical performance between 2005 and 2014 were assessed in regression models adjusting for age, sex, counties and clustering within general practices. RESULTS: Treatment targets were achieved in a higher proportion of patients in 2014 compared with 2005: hemoglobin A1c ≤7.0% (≤53 mmol/mol) in 62.8% vs 54.3%, blood pressure ≤135/80 mm Hg in 44.9% vs 36.6%, and total cholesterol ≤4.5 mmol/L in 49.9% vs 33.5% (all adjusted P≤0.001). Regarding screening procedures for microvascular complications, fewer patients had recorded an eye examination (61.0% vs 71.5%, adjusted P<0.001), whereas more patients underwent monofilament test (25.9% vs 18.7%, adjusted P<0.001). Testing for albuminuria remained low (30.3%) in 2014. A still high percentage were current smokers (22.7%). CONCLUSIONS: We found moderate improvements in risk factor control for patients with type 2 diabetes in general practice during the last decade, which are similar to improvements reported in other countries. We report major gaps in the performance of recommended screening procedures to detect microvascular complications. The proportion of daily smokers remains high. We suggest incentives to promote further improvements in diabetes care in Norway.

Glycemic control and complications in patients with type 1 diabetes - a registry-based longitudinal study of adolescents and young adults.

OBJECTIVE: The main aims of this study were to assess longitudinal glycemic control and the prevalence of retinopathy and nephropathy in young people (aged 14-30 yr) with type 1 diabetes in Norway. METHOD: Data on 874 patients were obtained by linking two nationwide, population-based medical quality registries: The Norwegian Diabetes Register for Adults and The Norwegian Childhood Diabetes Registry. RESULTS: Median age was 23 yr, median diabetes duration 9 yr and 51% were male. Median HbA1c increased through adolescence to peak at ages of 17 yr for females and 19 yr for males, females had higher HbA1c than males: 9.3% (78 mmol/mol) vs. 9.1% (76 mmol/mol). Subsequently, median HbA1c declined but was still >8% (>64 mmol/mol) for patients approaching 30 yr. Half of the patients aged 14-17 yr and 40% of patients aged 18-25 yr had HbA1c >9% (75 mmol/mol). Retinopathy was found in 16% and nephropathy in 13% of the population. Patients transferring from the pediatric department to adult care between the ages of 14 and 17 yr had higher median HbA1c and prevalence of late complications than those transferring at ages 18-22 yr. Less than 40% of patients with albuminuria were treated with ACE inhibitors or angiotensin II receptor blocker. CONCLUSION: Our results demonstrate that treatment of adolescents and young adults with type 1 diabetes in Norway is not optimal, especially for patients in their late teens. We suggest that pediatricians and endocrinologists should critically assess the care offered to this group and consider new approaches to help them improve glycemic control.

Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

BACKGROUND: Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. METHODS: Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. RESULTS: Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. CONCLUSIONS: For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.

Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison's disease: a randomized clinical trial.

CONTEXT: Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease. OBJECTIVE: The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy. DESIGN, PATIENTS, AND INTERVENTIONS: This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm. MAIN OUTCOME MEASURES: The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety. RESULTS: CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoL indices in the vitality domain improved over time with CSHI. No benefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters. CONCLUSION: CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy.

Treatment of type 1 diabetes in the specialist health service--data from the Norwegian Diabetes Register for Adults.

BACKGROUND: The Norwegian Diabetes Register for Adults was established in 2005. The aim of the study is to assess the quality of treatment for adult patients with type 1 diabetes in the specialist health service based on register data. MATERIAL AND METHOD: We included patients ≥ 18 years with type 1 diabetes in the specialist health service for whom the register has data for the period from 1 July 2010-to 31 December 2011. The patients were asked to consent to the transfer of data to the register when they attended a routine consultation. As of 31 December 2011, 95% of the patients asked gave their consent. It is not known how large a proportion of patients were asked. RESULTS: We included the last registered data for 3,697 patients (46.8% women) from 24 outpatient clinics and specialist centres. The average age was 41.8 years and the average duration of diabetes was 20.8 years. Median HbA1c, systolic blood pressure and LDL cholesterol were 8.0%, 126 mm Hg and 2.8 mmol/l respectively. 9.8% achieved all treatment targets set out in the national guidelines for diabetes. 18% had HbA1c ≤ 7.0%, while 22% had HbA1c ≥ 9%. 39% of patients on statin therapy achieved the treatment target for LDL cholesterol. 19.6% smoked on a daily basis. 14.9% had received treatment for retinopathy and 5.8% had experienced coronary heart disease. There was no record of foot examination or ophthalmoscopy being performed in 33% and 29% of patients. INTERPRETATION: The preliminary register data indicate that diabetes treatment should be improved both with respect to the implementation of recommended procedures and the proportion of patients who achieve the treatment targets.

Within-subject biological variation of glucose and HbA(1c) in healthy persons and in type 1 diabetes patients.

BACKGROUND: Several articles describing within-subject biological variation of fasting glucose and HbA(1c) in healthy populations have been published, but information about biological variation of glucose and HbA(1c) in patients with type 1 diabetes is scarce. It is reasonable to assume that type 1 diabetics differ from their healthy counterparts in this matter. The aim of our study was to estimate the biological variation of glucose and HbA(1c) in healthy subjects and in patients with type 1 diabetes. METHODS: Fifteen healthy individuals and 15 type 1 diabetes patients were included. Biological variations were calculated based on blood samples collected weekly for 10 consecutive weeks from the healthy and the eligible of the type 1 diabetes patients. RESULTS: The within-subject variations of glucose were approximately 5% in healthy individuals and 30% in diabetes patients, and for HbA(1c) they were 1.2% in healthy individuals and 1.7% in diabetes patients. CONCLUSIONS: In conclusion, we found a high within-subject biological variation of glucose in diabetes patients as expected compared to healthy individuals (30% vs. 5%). The short-term (2 months) within-subject biological variation of HbA(1c) did not differ significantly between well regulated type 1 diabetes patients and healthy individuals (1.7% vs. 1.2%).

Self-monitoring of blood glucose in type 1 diabetes patients with insufficient metabolic control: focused self-monitoring of blood glucose intervention can lower glycated hemoglobin A1C.

OBJECTIVE: Little attention has been given and few studies have been published focusing on how to optimize self-monitoring of blood glucose (SMBG) use to monitor daily therapy for persons with type 1 diabetes mellitus. This study was designed to evaluate the effect on glycated hemoglobin (A1C) of a structured intervention focused on SMBG in type 1 diabetes patients with insufficient metabolic control (A1C ≥8%) using a randomized clinical trial design. METHOD: One hundred fifty-nine outpatients with type 1 diabetes on multiple injection therapy with insulin and A1C ≥8% were recruited and randomized to one group receiving a focused, structured 9-month SMBG intervention (n=59) and another group receiving regular care based on guidelines (n=64). RESULTS: Glycated hemoglobin values (mean % ± standard deviation) at study start was similar: 8.65 ± 0.10 in the intervention group and 8.61 ± 0.09 in the control group. The two groups were comparable (age, gender, body mass index, complication rate, and treatment modality) at study start and had mean diabetes duration and SMBG experience of 19 and 20 years, respectively. At study end, there was decrease in A1C in the intervention group (p<.05), and the A1C was 0.6% lower compared with the control group (p<.05). No increase in the number of minor or major hypoglycemia episodes was observed in the intervention group during the study period. CONCLUSIONS: A simple, structured, focused SMBG intervention improved metabolic control in patients with longstanding diabetes type 1 and A1C ≥8%. The intervention was based on general recommendations, realistic in format, and can be applied in a regular outpatient setting.