Quality of Life and Treatment Satisfaction in Participants with Maturity-Onset Diabetes of the Young: A Comparison to Other Major Forms of Diabetes.

AIMS: We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. METHODS: A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent's perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. RESULTS: Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p<0.001). QoL was better in patients with HNF-MODY compared with patients with T1D (p=0.006), and they did not differ in terms of treatment satisfaction. CONCLUSIONS: QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.

How well we treat with insulin in the Czech Republic and in the Slovak Republic A summary of results and comments on the original Czech-Slovak DIAINFORM study.

Despite the continuously improving treatment options, many patients with type 1 (T1DM) and type 2 diabetes (T2DM) still do not achieve the recommended treatment goals. The article provides summary and commentary of the results of DIAINFORM study focused on the level of metabolic control in T1DM and T2DM patients treated with insulin in the Czech and Slovak Republics. The overall percentage of patients with HbA1c 3 mmol/mol in the T1DM group was 29.9 % and in the T2DM group was 33.4 %.

Current view of treatment of hypoglycemia.

Hypoglycemia is a side effect of the therapy primarily with insulin, sulphonylurea derivates and glinides. Its therapy is based on the immediate ingestion of sacharides, preferably glucose. Amount of 15-20 g is recommended as its optimal dose, although several recent studies are suggesting amount related to the patient´s weight. The therapy of severe hypoglycemia in the non-professional settings is based on glucagon injection, in the professional ones intravenous administration of glucose is preferable option.

Analysis of Postprandial Glycemia in Relation to Metabolic Compensation and Other Observed Parameters of Outpatients with Type 2 Diabetes Mellitus in the Czech Republic.

INTRODUCTION: The goal of the study was to determine the level of metabolic compensation expressed by glycosylated hemoglobin, fasting plasma glucose, and postprandial glucose as determined after a standardized breakfast; further, to evaluate interrelationships between the studied parameters and postprandial glucose levels. METHODS: The study included 1055 patients with type 2 diabetes mellitus. Their fasting plasma glucose and postprandial glucose were measured before and after a standardized breakfast. Attending diabetologists completed a uniform questionnaire that included demographic data, type of antidiabetic treatment, duration of diabetes, latest glycosylated hemoglobin value, presence of dyslipidemia, and organic complications. RESULTS: Glycosylated hemoglobin < 53 mmol/mol was achieved in 363 (34.2%), postprandial glucose < 7.5 mmol/l in 211 (19.9%), and fasting plasma glucose < 6 mmol/l in 251 (23.7%) patients. Excellent metabolic compensation, indicated by all the above mentioned glycosylated hemoglobin, fasting plasma glucose, and postprandial glucose values simultaneously, was achieved in only 71 (6.7%) patients. Comparable to fasting plasma glucose and postprandial glucose values, correlation with glycosylated hemoglobin levels is statistically significant; however, there is no difference at different glycosylated hemoglobin levels. There was a significant correlation between dyslipidemia and postprandial glycemia (p = 0.013). CONCLUSION: The objective of care for patients with diabetes mellitus is to improve their long-term metabolic compensation; to that end, both fasting plasma glucose and postprandial glucose deserve equal attention.

[Urinary iodine concentration in adult patients with type 1 diabetes mellitus]. / Jodurie u nemocných s diabetes mellitus 1. typu Vztahy k vybraným parametrum charakterizujícím diabetický syndrom.

INTRODUCTION: In patients with type 1 and 2 diabetes mellitus only rare data concerning the status of iodine supplementation and impact of possible iodine deficiency is available. AIM: To get basic information about (a) state of supply with iodine in patients with type 1 diabetes mellitus (DM1T), (b) the difference from non-diabetic population, (c) possible association of iodine saturation with some clinical and laboratory features of the diabetic syndrome, including the state of thyroid gland. SUBJECTS AND METHODS: We examined 54 men and 51 women treated with DM1T in a cross-sectional study. Age: median 42 years (25th quartil 31, 75th quartil 55), DM1T duration: 18 years (13, 23), BMI: 25.9 (23.3, 29.7), HbA1c: 61 mmol/mol (51, 71), creatinine: 71 µmol/l (61, 83), micro-albuminuria 4.3 µg/min (1.9, 11.8), TSH: 1.77 mIU/l (1.12, 2.80). The iodine saturation was evaluated using iodine concentration in a sample of first morning urine. RESULTS: Urinary iodine concentration in the whole group: median 152 µg/l, 25th quartile 117 µg/l, 75th quartile 219 µg/l. More than 50 % of the urinary iodine samples fell within range of optimal saturation (100-200 µg/l), 13 % within insufficient saturation (< 100 µg/l), 35 % of the samples showed increased saturation (> 200 µg/l), in which 2/3 were men. Using multiple regression analysis we found significant positive association of urinary iodine concentration and male gender, body weight, stature, and serum creatinine. No relation between urinary iodine and clinical and laboratory features of the diabetic syndrome was found. CONCLUSIONS: Iodine saturation in examined patients with DM1T was in accordance with ICCIDD (WHO) requirements for optimal/good saturation in non-diabetic population. With respect to the chosen normal urinary iodine concentration, eg. 100, resp. 150 µg/l the features of diabetic syndrome were not different. The question whether other factors than general measures taken in the past for solution of the iodine deficiency in the Czech Republic are involved in good level of iodine saturation in patients with DM1T should be addressed in further investigations comprising larger cohorts of patients.Key words: diabetes mellitus - urinary iodine concentration.

[Monitoring of diabetes compensation in patients treated with an insulin pump in the Czech Republic]. / Monitorování kompenzace diabetu u pacientu lécených inzulinovou pumpou v Ceské republice.

INTRODUCTION: Insulin pump treatment (IP) is one of the ways of intensive insulin therapy, designed preferentially for patients with type 1 diabetes. The price of the treatment is higher than that of the conventional basalbolus and insulin regimens using repeated insulin application with a dose selector. GOAL: Quality assessment of IP therapy monitoring in patients with DM in a representative sample of the patient population with DM kept in the database of the General Health Insurance Company of the Czech Republic (VZP) which provided health care coverage for 63% of Czech population in 2014. METHODOLOGY: We identified all individuals in the VZP database who had a record of DM diagnosis (E10-E16 based on ICD 10) or who had any antidiabetic therapy prescribed (ATC group A10) in the period of 2009-2013. Over the whole period of 2009-2014 there were overall n=4,002 unique patients with DM identified in the VZP data, who were treated with IP within the assessment period. Incidence for the year 2014 (the newly treated with an insulin pump): all patients who had IP recorded in 2014 while in the preceding period of 2009-2013 they had no record of IP use. Prevalence for the year 2014 (all treated with an insulin pump): all the patients who for the period of 2010-2014 had at least once insulin pump use recorded and who did not die before 2014. Quality control parameters (HbA1c examination and consumption of glucose level test strips) for patients treated with IP were only assessed in detail for the year 2014, namely for all patients undergoing insulin pump treatment in 2014 throughout the year (i.e. from 1 January 2014 to 31 December 2014), i.e. in n=3,189 patients in all. RESULTS: In 2014 there were 247 incident patients and 3 794 prevalent patients. IP was newly introduced for almost 50% of the patients aged 20-39 years. In 2014 an average frequency of HbA1c examination equaled 3.38 per patient and 98.5% patients were examined for HbA1c at least once. An average consumption of glucose level testing strips per patient was 879 pieces. CONCLUSION: The pilot project of assessment of quality parameters for IP therapy monitoring shows that the patients treated with IP have glycated hemoglobin checked quite frequently (3.38 checkups per patient in 2014) and they measure their blood glucose 2-3 times a day on average.

[The PROROK project results after 6 months of intervention (Prospective observation project focusing on the relevance of the difference between fasting blood glucose levels and postprandial blood glucose for estimation of success of type 2 diabetes therapy)]. / Výsledky projektu PROROK po 6 mesících intervence (Prospektivní observacní projekt významu diference glykemie nalacno a postprandiální glykemie pro odhad úspesnosti terapie diabetu 2. typu).

INTRODUCTION: The PROROK project (Prospective observation project focusing on the relevance of the difference between fasting and postprandial blood glucose levels for the estimation of success of type 2 diabetes therapy) had a character of non-interventional, prospective, multicentric observation study lasting 6 months, whose goal was to quantify the relevance of the difference between fasting and postprandial blood glucose levels to the success of the treatment with GLP1 receptor agonists, resp. the treatment with basal, premixed insulin, or a combination of basal-bolus insulin. Physicians chose a therapy for patients with insufficiently compensated problems as they considered appropriate; 4,972 patients were included. GOAL: Evaluation of the intervention results for the patients included in the PROROK observation project with a focus on the choice of therapy by the treating diabetologist after 6 months of observation. RESULTS: An average improvement of the glycated hemoglobin values in the whole cohort reached 1.6%, the median of the resulting glycated hemoglobin reached 5.9% and 5.8% resp. (basal insulin). Statistically significant was the change in the median weight in the cohort treated with GLP-1 receptor agonists, from 105 kg to 100 kg; this did not significantly change in the other cohorts. The change of waist circumference over time in all patients and in the individual cohorts was consistent with the change of weight. The median change of fasting blood glucose levels in the whole cohort was -1.7 mmol/l after 3 months and -2.4 mmol/l (p<0.001) after 6 months. The greatest absolute decrease was recorded in the cohort treated with basal insulin (-2.8 mmol/l). The median change of postprandial blood glucose levels was -2.4 mmol/l after 3 months and -3.3 mmol/l (p<0.001) after 6 months. The greatest absolute decrease was recorded in the branch treated with a combination of prandial and basal insulin (-3.9 mmol/l). All differences p<0.001. CONCLUSION: The choice of therapy in the PROROK project is in agreement with the basic findings in pathophysiology of type 2 diabetes and with the options of an individually chosen targeted intervention involving antidiabetic therapy. The results of the six-month observation have proven the individual choice of therapy correct. In the cohort of diabetic patients differing at the beginning in weight, waist circumference, fasting blood glucose and the difference between fasting and postprandial glucose levels, an individually chosen therapy led to the same final result, while an absolute change in the followed parameters differed in the individual groups.

[Do diabetologists choose a therapy rationally? Basic results of the PROROK project (a prospective observation project to assess the relevance of the difference between fasting glycemia and postprandial glycemia to estimation of success of type 2 diabetes therapy)]. / Volí diabetologové terapii racionálne? Základní výsledky projektu PROROK (Prospektivní observacní projekt významu diference glykemie nalacno a postprandiální glykemie pro odhad úspesnosti terapie diabetu 2. typu).

INTRODUCTION: The PROROK project (A prospective observation project to assess the relevance of the difference between fasting glycemia and postprandial glycemia to estimation of success of type 2 diabetes therapy) had a character of a non-interventional, prospective, multicentric observation project conducted for a period of 6 months, whose aim was to quantify the relevance of the difference between fasting and postprandial glycemia to the success of GLP1 receptor agonist treatment, or insulin therapy with basal or premixed insulin, or a combination of basal and bolus insulin. Physicians chose therapy for inadequately compensated patients at their own discretion, with 4 972 patients included. AIM: The study aimed at the assessment of the differences in basic anthropometric and biochemical parameters between the patient cohorts included in the PROROK project with regard to the therapy selected by the treating diabetologist. METHODOLOGY AND RESULTS: The patients treated with GLP1 receptor agonists were quite young, they have suffered from diabetes for a shorter period of time and at the same time were more obese and had the highest concentration of triacylglycerols. The patients who underwent basal insulin therapy, had the highest fasting glycemia. The patients for whom premixed insulin therapy or basal/bolus insulin regimen were chosen, manifested the highest postprandial glycemia, those with basal/bolus insulin regimen had the highest initial glycated haemoglobin. The difference between fasting and postprandial glycemia was the smallest in the cohort for which basal insulin therapy was chosen and the greatest in the cohort chosen for the therapy with premixed insulin, or with the basal/bolus insulin combination. Average improvement in glycated haemoglobin values reached 1.6 % within the whole cohort, a median of the resulting glycated haemoglobin reached 5.9 % or 5.8 % (GLP1 receptor agonist treatment). All the differences amounted to p < 0.001. CONCLUSION: Bearing in mind that the differences established in the parameters describing the cohorts, although statistically relevant, are of smaller clinical relevance, we regard as an important finding that the choice of therapy is in accordance with the basic knowledge about the pathophysiology of type 2 diabetes and possibilities of an individually chosen targeted intervention with antidiabetic therapy. We may conclude that most of the physicians participating in the PROROK project choose their therapy in a rational manner.

[POET2 registry: Comparison of annual direct medical costs of treating type 2 diabetes after addition of insulin NPH or insulin glargine to oral antidiabetic therapy in the Czech Republic]. / Registr POET2: srovnání prímých rocních zdravotnických nákladu na lécbu diabetu 2. typu po zahájení lécby inzulinem NPH nebo inzulinem glargin v kombinaci s perorálními antidiabetiky v Ceské republice.

INTRODUCTION: Poor glycemic control and the resulting development of complications of type 2 diabetes (DM2T) increase treatment costs. If adequate glycemic control cannot be achieved by lifestyle modifications and oral antidiabetic (OAD) therapy, initiation of insulin therapy is recommended. Cost effectiveness of basal insulins of the type NPH or glargine in combination with OAD for the treatment of DM2T was examined in a number of pharmacoeconomic studies. However, none of these studies were conducted in the Czech Republic. Therefore, the aim of the project POET2 was to compare annual direct medical costs of treating DM2T after addition of insulin NPH or glargine to OAD therapy in a clinical practice setting in the Czech Republic. METHODOLOGY: Data collected from 1967 patients who met the criteria for inclusion into the non-interventional prospective registry POET2 (DM2T, ongoing OAD therapy, glycated hemoglobin HbA1c > 6 % IFCC) and who were observed for 12 months following the start of insulin therapy (glargine: n = 1061 vs NPH: n = 906) were analysed. Costs of treatment were analysed from the perspective of health insurance companies and included costs of medication, medical devices and medical procedures. RESULTS: In both treatment groups a reduction of HbA1c (glargine group: by 1.77 % IFCC vs NPH group: by 1.73 % IFCC) and fasting plasma glucose (glargine group: by 3.67 mmol/l vs NPH group: by 3.63 mmol/l) was observed. Insulin glargine therapy was associated with the incidence of a significantly lower number of documented symptomatic hypoglycemic events (glargine group: 0.840 events per patient and year of treatment vs. NPH group: 1.053 events per patient and year of treatment; p < 0.05). Overall annual direct medical costs associated with the initiation of basal insulin treatment were higher on average by 2547.07 CZK among patients treated with insulin glargine (glargine group: 12173.09 ± 4169.44 CZK vs NPH group: 9626.02 ± 3432.79 CZK; p < 0.001) due to higher costs of medication (glargine group: 7992.97 ± 4001.81 CZK vs NPH group: 3784.2 ± 3181.48 CZK; p < 0.001). By contrast, costs of medical devices (glargine group: 2332.08 ± 917.84 CZK vs NPH group: 3893.95 ± 989.79 CZK; p < 0.001) and medical procedures (glargine group: 1848.04 ± 684.89 CZK vs NPH group: 1947.87 ± 685.43 CZK; p < 0.001) were lower among patients treated with insulin glargine. CONCLUSION: Addition of basal insulin to OAD therapy was an efficacious therapeutic intervention for the treatment of DM2T in a clinical practice setting in the Czech Republic. Overall annual direct medical costs were higher among patients treated with insulin glargine than among patients treated with insulin NPH. However, costs of medical devices and medical procedures were lower in the insulin glargine group. In addition, incidence of hypoglycemia was significantly lower among patients treated with insulin glargine.

[SOLOSTAR study demonstrated high levels of patient satisfaction with the use of the insulin pen SoloStar® in the Czech Republic]. / Studie SOLOSTAR prokázala vysoký stupen spokojenosti pacientu s pouzíváním inzulinového pera SoloStar® v Ceské republice.

INTRODUCTION: The aim of the observational, prospective and non-interventional survey SOLOSTAR was to obtain, in a clinical practice setting in the Czech Republic, information about patient satisfaction with the use of the pre-filled insulin pen SoloStar. METHODOLOGY: 1 805 patients suffering from type 1 or 2 diabetes who began using the pen SoloStar were observed for 3 to 4 months. Satisfaction of patients with SoloStar and with its particular features was evaluated in the group of all patients and in subgroups defined by demographic parameters including the type of handicap. Patients also compared SoloStar with the pens used before the entry into the survey. RESULTS: 98.3 % of patients rated overall satisfaction with the pen SoloStar as "excellent" and "good" (the highest and second highest rating on a 5-point scale). Demographic criteria, including visual handicap and manual dexterity handicap, did not have any statistically significant effect on the rating of the overall satisfaction with SoloStar. Features of SoloStar were rated as "excellent" and "good" by more than 90% of patients. Higher rating of some of the features of Solo-Star was awarded mostly by patients without prior experience with insulin application. Patients who used other insulin applicators before entering into the survey were more satisfied with the pen SoloStar than with the previously used applicator and most of them rated the use of SoloStar (93.1 %) and insulin application with SoloStar (83.5 %) as "much easier" and "easier" (the highest and second highest rating on a 5-point scale) in comparison with the previously used pen. CONCLUSION: The use of the pen SoloStar in a clinical practice setting in the Czech Republic is associated with high levels of satisfaction of patients, including handicapped patients. In addition, patients preferred SoloStar over insulin pens used before the entry into the survey.Key words: diabetes mellitus - insulin pen - patient satisfaction.

[Basal insulin glargine using a basal-bolus regimen in a common clinical practice: observational, non-interventional, multicenter, national project LINDA (Lantus in daily practice - safety and efficacy in basal bolus regimen)]. / Terapie inzulinem glargin v rezimu bazál/bolus v klinické praxi: observacní neintervencní multicentrický projekt LINDA (Lantus in daily practice - safety and efficacy in basal bolus regimen).

OBJECTIVE: To evaluate the safety and efficacy of basal insulin glargine using a basal-bolus regimen in a common clinical practice setting in the Czech Republic. PATIENTS AND METHODS: The LINDA project was a non-interventional, multicenter (n = 255), national, observational project. A total of 4,998 patients with Type 1 and 2 diabetes mellitus (T1DM, T2DM) with predominantly insulin therapy (99,7 %), after switch on insulin glargine at basal-bolus regimen, were enrolled in this project. The patients were followed up for 6 months after initiation of the therapy with insulin glargine. The primary objective of the project was to investigate the incidence of severe hypoglycemic episodes during the treatment with basal insulin analogue glargine (Lantus®) in a common clinical practice setting. The se-condary endpoints were changes in glycosylated hemoglobin (HbA1c) levels, fasting plasma glucose (FPG), body weight, insulin dose, change of number of hypoglycemic episodes in comparison the previous therapy and the frequency of adverse effects. RESULTS: Severe hypoglycaemia were observed during treatment with insulin glargine at 0.8 % patients. When comparing the incidence of hypoglycemia with the previous therapy, we demonstrated a clinically and statistically significant reduction in their frequencies. The percentage of patients with hypoglycemic episodes (17.6 %), severe hypoglycemia (0.8 %) and severe nocturnal hypoglycemia (0.3 %) over the last month of treatment with insulin glargine using the basal-bolus regimen was consistently lower compared to the last month of treatment before initiation of this therapy (42.5 %, 17.6 %, and 13.8 % of the patients, respectively). In patients with T1DM, the incidence of hypoglycemia decreased from 37.80 ± 15.95 episodes/patient/year to 8.76 ± 4.38 epi-sodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 5.64 ± 3.27 episodes/patient/year to 0.0396 ± 0.012 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 3.84 ± 2.04 episodes/patient/year to 0.0096 ± 0.003 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. In patients with T2DM, the incidence of hypoglycemia decreased from 12.48 ± 7.57 episodes/patient/year to 1.68 ± 0.78 episodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 2.04 ± 0.94 episodes/patient/year to 0.0132 ± 0.005 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 1.32 ± 0.77 episodes/patient/year to 0.0048 ± 0.0008 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. A statistically significant improvement in the metabolic control was demonstrated when using insulin glargine. The glycated hemoglobin (HbA1c) decreased from 7.74 ± 1.71 % to 6.43 ± 1.39 % ( -1.31 ± 0.32 %, p < 0.001) in patients with T1DM, and from 8.13 ± 1.56 % to 6.72 ± 1.40 % ( -1.41 ± 0.28 %, p < 0.001) in patients with T2DM. A statistically significant (p < 0.001) increase in the number of patients with HbA1c < 5.4 % was further demonstrated. The decrease in fasting blood glucose (FBG) and 6-point blood sugar profile was also statistically significant in both types of diabetes (p < 0.001). Changes in therapy and subsequent treatment with insulin glargine were perceived positively by both physicians and patients. CONCLUSION: In the common clinical practice setting, the initiation of treatment with insulin glargine using the basal-bolus regime in patients with previous insulin therapy resulted in a reduction in the incidence of hypoglycemic events, including severe hypoglycemia and severe nocturnal hypoglycemia, and improved metabolic control in patients with diabetes (reduced glycated hemoglobin, fasting glucose values and 6-point blood glucose profile). Greater satisfaction with the current treatment was reported by both patients and physicians.Key words: basal-bolus regimen - diabetes mellitus - insulin glargine - observational project.

[Diffuse idiopathic skeletal hyperostosis]. / Difuzní idiopatická skeletární hyperostóza.

Diffuse idiopathic skeletal hyperostosis is a progressive non-inflammatory bone and entheses disease which reduces the quality of life and self-sufficiency of patients. Despite significant prevalence is awareness of this disease still low and often leads to misdiagnosis. Therapeutic approach is different in diseases with similar symptomatology so it is important to raise awareness of this disease.

Comparison of glucose variability assessed by a continuous glucose-monitoring system in patients with type 2 diabetes mellitus switched from NPH insulin to insulin glargine: the COBIN2 study.

BACKGROUND: Glucose variability combined with glycosylated hemoglobin (HbA1c) assessments more reliably represents the level of glycemic control. The study was aimed to compare blood glucose variability with insulin glargine vs. neutral protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a continuous glucose-monitoring system (CGMS), in patients treated with basal insulin using stable dose of oral antidiabetic agents and HbA1c in the range of 4.5-8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2-9.4 % Diabetes Control and Complications Trial (DCCT) units]. METHODS: This was a multicenter, prospective, open-label, single-arm study in patients (N = 116) treated for ≥ 2 months with NPH and metformin combined with sulfonylurea or glinide. Glucose variability was measured after a 4-week NPH treatment phase and after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L · h)]. Differences (glargine-NPH) in AUC within 24 h in the glucose ranges of ≤ 3.3, ≤ 3.9, 7.5-3.9 (margins excluding), ≥ 7.5, ≥ 10, and ≥ 15 mmol/L were evaluated. Circadian fluctuation of glucose was assessed by M-value (log-transformation of the deviation from an arbitrary standard). RESULTS: AUCs of glucose in the lowest ranges (≤ 3.3 and ≤ 3.9 mmol/L) did not change significantly after treatment with glargine. Those in the higher ranges (≥ 7.5, ≥ 10, and ≥ 15 mmol/L) were significantly lower (p < 0.001 for all ranges), whereas AUC of glucose in the normal range (3.9-7.5 mmol/L) was significantly higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation of glucose assessed by M-value showed a significant decrease after glargine treatment (p < 0.003). No significant differences in hypoglycemia confirmed by glucose value ≤ 3.3 mmol/L were found between treatment phases. This trial is registered at ClinicalTrials.gov, NCT00659477. CONCLUSIONS: As monitored by CGMS, switching from NPH to glargine with active titration shifted glucose from abnormally high to normal levels with reduced fluctuation and without increased risk of hypoglycemia.