Dawn Phenomenon Research Articles

Contribution of Pancreatic Alpha-Cell Function to Insulin Sensitivity and Glucose Variability in Type 1 Diabetes Patients

In type 1 diabetes (T1D) patients, relationships between pancreatic alpha cell function and glucose metabolism remain elusive. Therefore, we aimed to reveal the contribution of alpha cell function to insulin sensitivity, hepatic glucose uptake (HGU), and glucose variability, including the dawn phenomenon, in T1D patients. We recruited forty Japanese T1D patients with a median (interquartile range) BMI of 21.0 (19.3-22.7) kg/m2, diabetes duration of 2.6 (0.1-10.3) years, and HbA1c level of 8.2 (7.4-10.3) %. We measured the arginine-stimulated glucagon secretion using RIA and double-sandwich ELISA and subsequently assessed the dawn phenomenon using an artificial pancreas (STG-55®, Nikkiso, Japan) and performed a hyperinsulinemic-euglycemic clamp followed by oral glucose loading to evaluate insulin sensitivity and HGU. Glycemic variability was analyzed with continuous glucose monitoring (CGM). The median areas under the curve of glucagon measured by RIA (AUCglcRIA) and ELISA (AUCglcELISA) were 3.7 (2.6-4.6) × 104 and 1.9 (0.8-4.3) × 103 pg/mL × min, respectively. The glucose infusion rate (GIR) during the euglycemic clamp was inversely correlated with AUCglcRIA and AUCglcELISA (R2 = 0.21 and 0.44, P = 0.033 and 0.038, respectively, adjusted for age, sex, and BMI). In addition, the median GIR was significantly lower in the high glucagon response group than in the low glucagon response group [7.3 (5.1-8.4) vs. 9.2 (7.0-11.7), P = 0.049]. The dawn index (ratio of insulin requirements between 4:00-8:00 and 0:00-04:00) and HGU did not correlate AUCglcRIA and AUCglcELISA. The standard deviation of glucose levels determined by CGM significantly correlated with AUCglcRIA (R2 = 0.28, P = 0.015) but not with AUCglcELISA (R2 = 0.01, P = 0.62). In conslusion, alpha cell function may contribute to insulin sensitivity in T1D, and its relationship with glycemic variability may be affected by the procedure of the glucagon assay used. Disclosure N. Takahashi: None. D. Chujo: Research Support; Self; Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Kyowa Hakko Kirin Co., Ltd.. H. Kajio: None. K. Ueki: Speaker's Bureau; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K., Novo Nordisk Inc., Mitsubishi Tanabe Pharma Corporation, Kyowa Hakko Kirin Co., Ltd., Takeda. Research Support; Self; Takeda, Astellas, Novo Nordisk Inc..

Insulin degludec is associated with less frequent and milder hypoglycemia in insulin-deficient patients with type 1 diabetes compared with insulin glargine or detemir.

The aim of this study was to determine the efficacy of insulin degludec (IDeg) relative to insulin glargine (IGlar) or insulin detemir (IDet) in glycemic control, as evaluated by continuous glucose monitoring (CGM) in insulin-deficient patients with type 1 diabetes. We studied 28 outpatients treated with IGlar or IDet (IGlar/IDet). Basal insulin was switched to IDeg when glycemic control was considered unstable, as judged by the dawn phenomenon or nocturnal hypoglycemia. Whole-day CGM data were also divided into daytime and nighttime data. The dawn phenomenon or nocturnal hypoglycemia under IGlar/IDet treatment was observed in all patients. Among 26 patients who completed the study, there were no significant differences in parameters representing glycemic variability, hyperglycemia, mean glycemic control, and HbA1c or insulin therapy-related quality of life at the night score. Measures of hypoglycemia [whole-day %Low and area under the curve (AUC) below 70] were significantly lower under IDeg treatment than under IGlar/IDet treatment (%Low, 9.6±11.5 vs. 14.7±14.9%, p=0.045; AUC below 70, 85.5±126.0 vs. 145.0±178.6mg/dlh, p=0.030). Dividing patients into two groups according to percentage or degree of hypoglycemia under IGlar/IDet treatment, the whole-day, daytime and nighttime %Low in the high-percentage groups and AUC below 70 in the high-degree groups were significantly ameliorated, respectively (p<0.05). Patients with unstable glycemic control under IGlar/IDet treatment did not improve glycemic control upon switching to IDeg, but the frequency and the degree of hypoglycemia was reduced in insulin-deficient outpatients with type 1 diabetes, especially in those suffering from severe hypoglycemia.

Poor Sleep Quality Is Associated with Dawn Phenomenon and Impaired Circadian Clock Gene Expression in Subjects with Type 2 Diabetes Mellitus.

Aims. We investigated whether poor sleep quality is associated with both dawn phenomenon and impaired circadian clock gene expression in subjects with diabetes. Methods. 81 subjects with diabetes on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index. The magnitude of dawn phenomenon was quantified by its increment from nocturnal nadir to prebreakfast. Peripheral leucocytes were sampled from 81 subjects with diabetes and 28 normal controls at 09:00. Transcript levels of circadian clock genes (BMAL1, PER1, PER2, and PER3) were determined by real-time quantitative polymerase chain reaction. Results. The levels of HbA1c and fasting glucose and the magnitude of dawn phenomenon were significantly higher in the diabetes group with poor sleep quality than that with good sleep quality. Peripheral leucocytes from subjects with poor sleep quality expressed significantly lower transcript levels of BMAL1 and PER1 compared with those with good sleep quality. Poor sleep quality was significantly correlated with magnitude of dawn phenomenon. Multiple linear regression showed that sleep quality and PER1 were significantly independently correlated with dawn phenomenon. Conclusions. Dawn phenomenon is associated with sleep quality. Furthermore, mRNA expression of circadian clock genes is dampened in peripheral leucocytes of subjects with poor sleep quality.

Self-Monitoring of Blood Glucose to Assess Dawn Phenomenon in Chinese People with Type 2 Diabetes Mellitus.

Aims. We investigated whether self-monitoring of blood glucose could be used to assess dawn phenomenon in Chinese people with type 2 diabetes mellitus (T2DM). Methods. A total of 306 people with T2DM underwent continuous glucose monitoring and self-monitoring of blood glucose for 72 h. A linear model was used to fit the optimal linear formula of the magnitude of dawn phenomenon (ΔDawn) and self-monitoring of blood glucose values. Results. The prevalence of dawn phenomenon was similar within different oral antidiabetic drug groups (42.5%, 31.5%, and 40.9%, P = 0.216). Multiple variable linear regression showed that prebreakfast, prelunch, and predinner glucose measurements were independently and significantly correlated with ΔDawn. The linear formula between ΔDawn and blood glucose was as follows: ΔDawn (mg/dL) = 0.557 × prebreakfast − 0.065 × prelunch − 0.164 × predinner − 20.894 (mg/dL) (adjusted R2 = 0.302, P = 0.000). Conclusions. Dawn phenomenon could be partly assessed by blood glucose self-monitoring in Chinese people with T2DM using the abovementioned formula. The incidence of dawn phenomenon was similar among patients in different oral antidiabetic drug groups.

Effect of one week of CPAP treatment of obstructive sleep apnoea on 24-hour profiles of glucose, insulin and counter-regulatory hormones in type 2 diabetes.

Studies examining the impact of CPAP treatment on glycaemic control have yielded conflicting results, partly because of insufficient nightly CPAP use. We examined the 24-hour profiles of glucose, insulin and counter-regulatory hormones in 12 subjects with type 2 diabetes and OSA before and after 1 week of effective in-laboratory CPAP therapy over an entire 8-hour night thus ensuring optimal CPAP compliance. Blood samples were collected every 15 to 30 minutes for 24 hours under controlled conditions. The 24-hour mean glucose decreased from 153.2 ± 33.0 to 139.7 ± 24.2 mg/dL with CPAP (-13.5 ± 13.5 mg/dL; P = .005) without change in insulin levels. Morning fasting glucose levels decreased by 14.6 ± 3 mg/dL (P = .001) and the dawn phenomenon decreased by 7.8 ± 9.8 mg/dL (P = .019). CPAP treatment decreased norepinephrine levels while the 24-hour profiles of growth hormone and cortisol remained unchanged. In conclusion, 1 week of effective treatment of OSA over an entire 8-hour night results in a clinically significant improvement in glycaemic control via an amelioration of evening fasting glucose metabolism and a reduction in the dawn phenomenon, a late-night glucose increase that is not adequately treated by oral medications. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01136785.

Spontaneous and transient predinner hyperglycemia in some patients with diabetes: Dusk phenomenon.

Blood glucose fluctuations have higher risk than absolute blood glucose level in diabetic chronic complications. At present, “dawn phenomenon” is well known by clinicians, but “dusk phenomenon” has not been recognized. This study explored the objective existence of “dusk phenomenon” (spontaneous and transient predinner hyperglycemia) and its clinical significance.The data of 54 patients with diabetes, who received routine insulin pump therapy between December 2010 and October 2012 in our hospital, were retrospectively analyzed. These patients included 4 patients with type 1 diabetes mellitus (DM) (T1DM) and 50 patients with type 2 DM (T2DM). According to the difference between predinner and postlunch blood glucose levels, the 50 patients with T2DM were divided into dusk phenomenon group (4 patients, all the differences ≥0 mmol/L during insulin pump therapy), nondusk phenomenon group (12 patients, all the differences <0 mmol/L during insulin pump therapy), and suspicious group (34 patients, the differences were uncertain during insulin pump therapy). In the 4 patients with T1DM of this study, the differences all were more than 0 mmol/L during insulin pump therapy. The changes in blood glucose levels were observed, and the correlations of blood glucose level with other factors were analyzed in T1DM and T2DM patients, respectively.In T1DM patients, blood glucose level was significantly higher in predinner than in prebreakfast and prelunch (all P < 0.01), and in postdinner 2 hour than in postlunch 2 hour (P = 0.021). The predinner blood level had no significant correlations with the blood glucose level at other time points and insulin dosages (all P > 0.05). In T2DM patients, the predinner blood glucose level was significantly higher in dusk phenomenon group than in suspicious group and nondusk phenomenon group (all P < 0.05). In dusk phenomenon group, the blood glucose level remained rising from predinner to prebed, and the predinner blood glucose level was only significantly correlated with postdinner 2-hour blood glucose level (P < 0.05).The “dusk phenomenon” (spontaneous and transient predinner hyperglycemia) is an objective existence in some patients with diabetes. The predinner hyperglycemia can affect blood glucose control between postdinner and prebed. Awareness of the “dusk phenomenon” has important clinical significance.

The correlation of dawn phenomenon with glycemic variability parameters in type 2 diabetes mellitus

Abstract Introduction. Dawn phenomenon could have deleterious effect on overall glycemic control. Glycemic variability may be an independent risk factor for the development of diabetes chronic complications. The study aimed to evaluate any correlations between the dawn phenomenon and parameters of glycemic variability in a cohort of type 2 diabetes patients (T2DM). Material and methods. This retrospective observational study included 131 T2DM patients. Continuous glucose monitoring (CGM) has been performed. Data from the first 24h of full recording were used for analysis of glycemic variability indices: mean level of 24h interstitial glucose value and standard deviation; % coefficient of variation; J index; mean amplitude of glycemic excursion - MAGE; continuous overall net glycemic action (CONGA) at 1, 2, 4 and 6 hours; mean of daily differences (MODD) index. Results. Mean age was 56.04 ± 9.91 years, 35.9% women, 17.6% on diet, 53.4% on oral therapy and 29% on insulin. Dawn phenomenon was more frequent in patients below 60 years (70%) and in oral therapy group (72.85%). Significant correlations between the dawn phenomenon and j-index, MAGE, CONGA-4 and CONGA-6 have been found in T2DM patients on diet therapy alone. The amplitude of dawn phenomenon was 46.10 ± 24.40 mg/dl and significantly correlated (p&lt;0.05) after adjustment for age, gender and treatment with % CV, MAGE, CONGA-1, CONGA-2, CONGA-4, CONGA-6 and MODD. Conclusions. The dawn phenomenon significantly increases the glycemic variability parameters in drug-naive T2DM patients, with no impact in T2DM on oral or insulin therapy.

The comparison of different quantitative criteria of the Dawn Phenomenon and its impact on blood glucose fluctuation in type 2 diabetes

A total of 128 individuals with type 2 diabetes underwent continuous glucose monitoring for 3 consecutive days. The dawn phenomenon was defined by three different parameters according to the previous research: (1)the absolute increase of glucose level from nocturnal nadir to prebreakfast value(∂G) above 20 mg/dl; (2)∂G above 10 mg/dl; (3)insulin requirement increased at least 20%. The participants were secondarily separated by presence/absence of a dawn phenomenon based on the definitions above. The impact on blood glucose fluctuation of different groups was assessed according to the standard deviation of blood glucose(SDBG), the area under curve above 10 mmol/L(AUC), and the mean amplitude of glycemic excursions(MAGE), etc. The frequencies of dawn phenomenon were 64.8%(∂G≥20mg/dl), 85.2%(∂G≥10 mg/dl), and 59.4%(rise in insulin requirement≥20%)respectively. The impacts on SDBG, AUC, MAGE, and MODD were without statistical difference(P>0.05) between the presence and absence of the dawn phenomenon patients when ∂G≥10 mg/dl. However, the differences reached statistical significance(P<0.05) when ∂G≥20 mg/dl and the increase in insulin requirement≥20%. Besides, the incidence of dawn phenomenon was positively correlated with HOMA-IR, HbA1C, and free C-peptide. Dawn phenomenon is a very frequent event in type 2 diabetes and not only impacts the overall glycemic control but also exaggerates glucose fluctuation. To be clinically relevant, ∂G≥20mg/dl should be taken as the quantitative criterion of the dawn phenomenon. (Chin J Endocrinol Metab, 2016, 32: 117-120) Key words: Diabetes mellitus, type 2; Dawn phenomenon; Incidence; Continuous glucose monitoring system; Blood glucose fluctuation

Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy.

Achieving near normal glucose homeostasis implies that all components of dysglycemia that are present in diabetes states be eliminated. Reducing ambient/overall hyperglycemia is a pre-requisite to eliminate the risk of development and progression of diabetes complications. More controversially however, are the relative and related contributions of postprandial glucose excursions, glucose variability, hypoglycemia and the dawn phenomenon across the spectrum of dysglycemia. For instance, it is likely that the dawn phenomenon contributes to ambient hyperglycemia and that postprandial glucose excursions are at the cross road of ambient hyperglycemia and glucose variability with glucose fluctuations as causative risk factors for hypoglycemia. Proof-of-concept trials such as the ongoing FLAT-SUGAR study are necessary for gaining further insight into the possible harmful effects of some of these features such as excessive glycemic variability and glucose excursions, still considered to be of minor relevance by several diabetologists. Whether their role will be more thoroughly proven through further intervention trials with "hard" endpoints, remains to be seen. In the meantime more consideration should be given to medications aimed at concomitantly reducing ambient/overall hyperglycemia and those additional abnormal glycemic features of dysglycemia.

Correlation study between obesity and dawn phenomenon in patients with type 2 diabetes

To investigate the correlation between the frequency of dawn phenomenon and obesity in patients with type 2 diabetes. This study was conducted in 98 patients with type 2 diabetes admitted to the Metabolic Disease Hospital of Tianjin Medical University from 2011 to 2014. The subjects were divided into 3 groups according to BMI: the normal weight (BMI 18.5-23.9 kg/m(2), n = 30), the overweight(BMI 24-27.9 kg/m(2), n = 33)and the obesity (BMI ≥ 28.0 kg/m(2), n = 35). All participants underwent continuous glucose monitoring for 72 h. Fasting plasma glucose(FPG), insulin and C-peptide were tested. Frequency of dawn phenomenon among the 3 groups was calculated, and the correlations between dawn phenomenon and its related factors were analyzed. The frequency of dawn phenomenon in type 2 diabetes increased with the increase of BMI in the 3 groups (P < 0.05) with 33.3% in the normal weight, 78.8% in the overweight and 88.6% in the obesity groups, respectively. The dawn phenomenon was positively correlated with BMI (r = 0.424, P < 0.05), Homeostasis model assessment of insulin resistance(HOMA-IR) (r = 0.781, P < 0.05), waist circumference (r = 0.394, P < 0.05), fasting C-peptide (r = 0.254, P < 0.05)and TG (r = 0.220, P < 0.05). It was negatively correlated with the course of diabetes mellitus (r = -0.278, P<0.05) and HDL-C (r = -0.268, P < 0.05). No correlation could be viewed between the dawn phenomenon and age, LDL-C, glycosylated hemoglobin A1c(HbA1c), TC and FPG (P > 0.05). The dawn phenomenon is closely associated with obesity and insulin resistance. The frequency of dawn phenomenon increases with BMI.

Suboptimal metabolic control and decompensation in children and adolescents with diabetes mellitus type 1

Aim of the study is identifying the causes of decompensation of metabolism in children with different levels of HbA1c by studying daily glycemic profiles using a continuous monitoring system (CGMS, Medtronic MiniMed, USA). Materials and methods . Blood glucose of 207 type 1 diabetes children with different compensation level was researched by continuous glucose monitoring system (СGMS). Statistical processing of the results was carried out using XLSTATS 4.0 program. Results. The causes of diabetes suboptimal control were deficit of bolus insulin doses in 53%, «dawn phenomenon» in 23%, hidden night hypoglycemia in 26%. Patients with HbA1c level higher than 9% have deficit short acting and basal insulin that was the cause of bad metabolic control. The compare of selfcontrol results and CGMS data was preformed and pointed the importance of glucose monitoring system for decompensation causes identification.

The influence of continuous subcutaneous insulin infusion therapy vs. multiple daily injections upon the diet of those with Type 1 diabetes: A food diary investigation

There exist a number of therapeutic options for the management of Type 1 diabetes (T1D). Multiple daily injections (MDI) are one such treatment and involve 4-5 daily subcutaneous injections of insulin. This frequently used approach is widely regarded as an effective method of controlling glycaemia; however, if a patient continues to suffer disabling episodes of hypoglycaemia, or if HbA1c remains above 8.5% continuous subcutaneous insulin infusion (CSII) may instead be recommended1. This therapy employs a small programmable pump device to facilitate the administration of insulin to the patient via a cannula. Various advantages of CSII have been documented compared to MDI, including improvements in glycaemic control and reduced incidence of both hypoglycaemia and the dawn phenomenon. An additional attribute, characterised by the flexible nature of the therapy, is that a liberalised diet may be enjoyed by patients, which in turn may infer potential nutrition and quality of life aberrations. This phenomenon is surprisingly under researched and further investigations to inform both treatment and risk would therefore be beneficial. Following ethical approval and informed consent patients with T1D using either CSII or MDI from the Royal Liverpool Hospital were asked to complete a 5 day weighed food diary. Dietplan 6 software was used to process the responses and demographic data from participants’ medical records were added to the dataset. All data were then interrogated using descriptive statistics and any non-normal data were transformed logarithmically before further enquiry with t-tests or analysed non-parametrically with Mann-Whitney-U-tests. The sample comprised of 20 patients (35% male, 65% female) with 11 using CSII and 9 using MDI. The patients’ mean age was 49±16 years and the majority were overweight or obese (72.7% CSII, 55.6% MDI). Nutrient Amount per day (CSII group) Amount per day (MDI group) % energy intake per day (CSII group) % energy intake per day (MDI group) Energy 1866.6 Kcal 2110.5 Kcal N/A N/A Protein 69.0 g/day 89.9 g/day 14.8 17.0 Total CHO 232.3 g/day 251.8 g/day 46.7 44.7 Total sugars 99.8 g/day 88.6 g/day 20.0 15.7 Total fat 73.5 g/day 80.1 g/day 35.4 34.2 Saturated fat 31.6 g/day 29.8 g/day 15.2 12.7 Table. Selected food diary results from patients using CSII and MDI compared to reference nutrient intakes. Results showed mean energy intake was below the reference nutrient intake (RNI) for the CSII group; potentially suggestive of underreporting (Table)3. Patients using both CSII and MDI consumed protein above the RNI; however, this macronutrient contributed towards 14.8% of the daily energy intake of patients using CSII and 17.0% of those using MDI3. Total carbohydrate (CHO) consumption was below the RNI of 50%; however, it should be noted that consumption of total sugars was above the RNI for males and females in both groups4. Previous research by the authors suggesting habitual fruit consumption, particularly in those using CSII, may explain this5. Total fat and saturated fat consumption was mostly synonymic with RNI’s. Although no statistically significant associations were seen between any of the variables and the diets of the two populations appeared largely homogenous it is reassuring that no detrimental changes occurred. Despite this further analysis of total energy, protein and CHO quality is warranted.

Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver.

Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production-related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.

Somogyi effect as the most common cause of fasting hyperglycemia in T1D patients

Materials and methods We analyzed the glycemic profile measured by 72h-CGMS in 85 patients with T1D (29 female), resulting in 255 overnight periods. We assessed the nocturnal glycemic profile and the accuracy of the CGMS sensor per night. Fasting hyperglycemia was categorized into dawn phenomenon when there was no nocturnal hypoglycemia followed by a minimum 10mg/dL rise plasma between 4: 00h-7: 00h; Somogyi effect when nocturnal hypoglycemia (< 70mg/dL) between 0: 00h-3: 00h was followed by morning hyperglycemia and poor glycemic control when there was sustained overnight hyperglycemia. Clinical data (age, diabetes duration, insulin regime, and HbA1c values) were obtained by chart review and compared to the different causes of fasting hyperglycemia.

Caracterización epidemiológica de pacientes diabéticos en terapia con infusión subcutánea continua de insulina y monitorización continua de glucosa en tiempo real

ObjectiveTo describe baseline characteristics of diabetic patients who were started on insulin pump and real time continuous glucose monitor (CSII-rtCGM) in a specialized center in Medellin, Colombia. Materials and methodsAll patients with diabetes with complete data who were started on CSII-rtCGM between February 2010 and May 2014 were included. This is a descriptive analysis of the sociodemographic and clinical characteristics. Results141 of 174 patients attending the clinic were included. 90,1% had type 1diabetes (T1D). The average age of T1D patients at the beginning of therapy was 31,4 years (SD 14,1). 75.8% of patients had normal weight (BMI<25), 21.0% were overweight (BMI 25-30) and 2,3% were obese (BMI>30). The median duration of T1D was 13 years (P25-P75=10.7-22.0). 14,2% of the patients were admitted at least once in the year preceding the start of CSII-rtCGM because of diabetes related complications. Mean A1c was 8.6%±1.46%. The main reasons for starting CSII-rtCGM were: poor glycemic control (50.2%); frequent hypoglycemia, nocturnal hypoglycemia, hypoglycemia related to exercise, asymptomatic hypoglycemia (30.2%); severe hypoglycemia (16.44%) and dawn phenomena (3.1%). ConclusionBaseline characteristics of patients included in this study who were started on CSII-rtCGM are similar to those reported in the literature. The Clinic starts CSII-rtCGM mainly in T1D patients with poor glycemic control, frequent or severe hypoglycemia despite being on basal/bolus therapy.

Epidemiological characterization of diabetic patients on therapy with continuous subcutaneous insulin infusion and continuous glucose monitoring in real time

Abstract Objective To describe baseline characteristics of diabetic patients who were started on insulin pump and real time continuous glucose monitor (CSII-rtCGM) in a specialized center in Medellin, Colombia. Materials and methods All patients with diabetes with complete data who were started on CSII-rtCGM between February 2010 and May 2014 were included. This is a descriptive analysis of the sociodemographic and clinical characteristics. Results 141 of 174 patients attending the clinic were included. 90.1% had type 1 diabetes (T1D). The average age of T1D patients at the beginning of therapy was 31.4 years (SD 14.1). 75.8% of patients had normal weight (BMI 30). The median duration of T1D was 13 years (P25–P75 = 10.7–22.0). 14.2% of the patients were admitted at least once in the year preceding the start of CSII-rtCGM because of diabetes related complications. Mean A1c was 8.6% ± 1.46%. The main reasons for starting CSII-rtCGM were: poor glycemic control (50.2%); frequent hypoglycemia, nocturnal hypoglycemia, hypoglycemia related to exercise, asymptomatic hypoglycemia (30.2%); severe hypoglycemia (16.44%) and dawn phenomena (3.1%). Conclusion Baseline characteristics of patients included in this study who were started on CSII-rtCGM are similar to those reported in the literature. The Clinic starts CSII-rtCGM mainly in T1D patients with poor glycemic control, frequent or severe hypoglycemia despite being on basal/bolus therapy.

Progress in the study of dawn penomenon and extended dawn phenomenon in patients with diabetes

Thedawn phenomenonis a term used to describe hyperglycemia or an increase in the amount of insulin needed to maintain normoglycemia, occurring in the absence of antecedent hypoglycemia, during the early morning hours, and mostly affecting children with type 1 diabetes. Currently, hyperglycemia before breakfast time is defined as dawn phenomenon, and postbreakfast abnormal hyperglycemia is referred as the extended dawn phenomenon. Dawn phenomenon is regarded as the result of the β cell dysfunction, which increased endogenous glucose production and the persistent insulin resistance. By using continuous glucose monitoring technology, dawn phenomenon can be effectively identified: The difference between the lowest glucose level during nocturnal time and the glucose value before breakfast over 1.11 mmol/L. And the long-acting insulin analogs and insulin pump are effective treatments for dawn phenomenon. (Chin J Endocrinol Metab, 2015, 31: 739-742) Key words: Dawn phenomenon; Extended dawn phenomenon; Continuous glucose monitoring

A preliminary study of pathogenesis of dawn phenomenon in patients with type 2 diabetes mellitus

Objective To study the preliminary pathogenesis of dawn phenomenon in patients with type 2 diabetes mellitus. Methods Two-hundred and sixty-four patients with type 2 diabetes had performed continuous glucose monitoring since Jan 2012 to July 2014. They were divided into two groups: patients without dawn phenomenon and patients with dawn phenomenon. Biochemical indicators including liver and kidney function, blood lipids, HbA1C, fructosamine(FMN), adrenocorticotropic hormone and cortisol were detected in the two groups. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed. The differences in biochemical indicators, glucose level and α-cell and β-cell function after fasting and glucose-load were compared. The correlation and regression analysis were performed between dawn phenomenon and other indicators. Results The level of adrenocorticotropic hormone, cortisol, HbA1C, FMN, the increment of fasting glucose and nocturnal nadir glucose(BG1), the glucose increment before and after breakfast(BG2), 24-hour mean glucose, duration above high limit, and HOMA-IR were significantly higher in patients with dawn phenomenon compared to those in patients without dawn phenomenon[(6.6±2.4)vs(4.8±1.9)pmol/L, (523.8±84.2)vs(448.2±76.9)nmol/L, (8.1±2.0)% vs (7.5±1.8)%, (0.32±0.09)vs(0.29±0.08)mmol/L, (26.2±5.8)vs(18.0±4.9)mg/dl, (39.6±8.3)vs(28.8±7.4)mg/dl, (188.5±36.2)vs(164.5±31.2)mg/dl, 29∶31(41%)vs 20∶10(28%), 4.18±0.94 vs 3.82±0.82](all P<0.05). ISI and AUCG/AUCI were lower in patients with dawn phenomenon than those in patients without dawn phenomenon(-4.28±0.62 vs -4.04±0.54, -0.74±0.48 vs -0.63±0.30)(all P<0.05). The level of glucagon at each time point and area under curve of glucagon were significantly higher in patients with dawn phenomenon than those in patients without. 0, 60, 180 min glucagon/insulin ratio and 0, 30, 120, 180 min glucagon/glucose ratio were significantly higher in patients with dawn phenomenon(all P<0.05). Logistic regression analysis showed that dawn phenomenon was positively related to HOMA-IR, glucagon/insulin ratio, BG2, BG1and cortisol(all P<0.05), and negatively related to ISI(P<0.05). Conclusion Dawn phenomenon may be associated with increased secretion of cortisol and dysfunction of islet α-cell and β-cell. (Chin J Endocrinol Metab, 2015, 31: 492-496) Key words: Diabetes mellitus, type 2; Dawn phenomenon; Cortisol; Islet α-cell; Islet β-cell

Somogyi Effect in a Patient of Type 2 Diabetes Mellitus

Morning hyperglycemia in diabetic subjects may be caused by the dawn phenomenon, or the Somogyi effect, or poor glycemic control. The dawn phenomenon is a normal rise in blood sugar as a person’s body prepares to wake up. In the early morning hours, hormones (growth hormone, cortisol and catecholamines) cause the liver to release large amounts of sugar into the bloodstream. For most people, the body produces insulin to control the rise in blood sugar. If the blood sugar level drops too low in the early morning hours, hormones (such as growth hormone, cortisol, and catecholamines) are released. These help reverse the low blood sugar level but may lead to blood sugar levels that are higher than normal in the morning. If the body doesn’t produce enough insulin, blood sugar levels can rise. This may cause high blood sugar in the morning (before eating). Somogyi effect occurs in a person who takes insulin doesn’t eat a regular bedtime snack, and the person’s blood sugar level drops during the night. The person’s body responds to the low blood sugar by releasing hormones that raise the blood sugar level. This may cause a high blood sugar level in the early morning. The dawn phenomenon is more common than the Somogyi effect. To diagnose these phenomena, it is useful to measure plasma glucose levels for several nights between 2 a.m. and 5 a.m. or use a continuous glucose monitoring system.

Effect of Growth Hormone on Dawn Phenomenon in Healthy Adults

The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.