Severe Nocturnal Hypoglycemia Research Articles

Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia.

Various endocrine dysfunctions occur during chemotherapy, including hypoglycemia. However, reports of hypoglycemia associated with 6-mercaptopurine (6-MP) are rare. Herein, we report an 8-year-old boy with severe symptomatic hypoglycemia likely due to 6-MP during chemotherapy. He had been diagnosed with acute lymphoblastic leukemia 3 years previously and was in the maintenance chemotherapy period. Treatment included oral dexamethasone, methotrexate, and 6-MP, of which only 6-MP was administered daily. Hypoglycemic symptoms appeared mainly at dawn, and his serum glucose dropped to a minimum of 37 mg/dL. Laboratory findings showed nothing specific other than increased serum cortisol, free fatty acids, ketone, alanine aminotransferase, and aspartate aminotransferase. Under the hypothesis of hypoglycemia due to chemotherapy drugs, we changed the time of 6-MP from evening to morning and recommended him to ingest carbohydrate-rich foods before bedtime. Hypoglycemia improved dramatically, and there was no further episode during the remaining maintenance chemotherapy period. To the best of our knowledge, this is the first report of this type of hypoglycemia occurring in an Asian child including Korean.

Estimating the utility value of hypoglycaemia according to severity and frequency using the visual analogue scale (VAS) and time trade-off (TTO) survey.

The primary objective of this study was to estimate the health utility values for hypoglycaemia events according to their severity and frequency. The secondary objective was to compare the health utilities between those with Type 2 Diabetes Mellitus and the general population. The health utilities of hypoglycaemia event were measured using Visual Analogue Scale (VAS) and Time Trade-Off (TTO) methods among conveniently sampled consenting adults (>18years and literate in either English or Malay language), which were then divided into two groups: those in the general population (GP) and those with Type 2 Diabetes Mellitus (T2DM). Each respondent was required to value 13 different health states, including frequencies of daytime hypoglycaemia and nocturnal hypoglycaemia, each depending on its severity (non-severe or severe). 256 respondents from the GP and 99 respondents with T2DM completed the survey. The T2DM group gave higher VAS-values compared to the GP group. The highest mean VAS-utility value for non-severe nocturnal hypoglycaemia occurring once monthly was 0.543 (SD 0.161), and for severe daytime hypoglycaemia occurring once quarterly was 0.293 (SD 0.162) which was the lowest utility value compared to other health states. However, non-severe nocturnal hypoglycaemia occurring once quarterly was 0.537 (SD 0.284) and has the highest TTO-utility value. Severe nocturnal hypoglycaemia occurring once quarterly has the lowest utility value which was -0.104 (SD 0.380). Daytime hypoglycaemia has lower utility value compared to nocturnal hypoglycaemia. Severe hypoglycaemia has a greater disutility compared with the non-severe hypoglycaemia in both studied groups. The findings show that as a health utility, hypoglycaemia has a substantial impact on utility with severe hypoglycaemia having a greater negative impact compared to non-severe events across the board. This highlights the importance of preventing development of severe hypoglycaemia in patients with Type 2 Diabetes Mellitus at any time of the day.

Cardiovascular Outcomes Trials Update: Insights from the DEVOTE Trial.

The DEVOTE study compared the cardiovascular safety of two basal insulins, degludec, and glargine U100 in patients with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). In this review, we summarize the results of DEVOTE and provide a clinical perspective. DEVOTE was a phase 3b, multicenter, international, treat-to-target, double-blind, event-driven trial. Patients with T2D > 50years of age with prior CVD or > 60years of age with CVD risk factors were randomly assigned to receive either degludec (n= 3818) or insulin glargine U100 (n= 3819) and were followed until at least 633 positively adjudicated major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) accrued. At baseline, the mean age of the subjects was 65.0years, the mean duration of diabetes was 16.4years, and the mean HbA1c was 8.4 ± 1.7%. After a median follow-up of 2years, HbA1c had decreased to 7.5 ± 1.2% in each group. Degludec was non-inferior to insulin glargine U100 with respect to the primary MACE outcome (hazard ratio 0.91; 95% CI 0.78-1.06). Significantly, lower rates of severe hypoglycemia and nocturnal severe hypoglycemia were observed with degludec compared to glargine U100 (rate ratios of 0.60; 95% CI 0.48-0.76 and 0.47; 95% CI 0.31 to 0.73, respectively). DEVOTE demonstrated that the cardiovascular safety of degludec was comparable to that of insulin glargine U100 in patients with T2D at high risk for CVD. Additionally, degludec was superior to insulin glargine U100 with respect to the risk for severe hypoglycemia. These results suggest that degludec might be preferred in patients at risk for severe hypoglycemia, including the elderly, those with CVD and/or those with chronic kidney disease.

Initiating Basal Insulin Supported Oral Therapy (BOT) with Insulin Glargine 300 U/mL (Gla-300) Improves Glycemic Control in Patients (Pts) with Type 2 Diabetes (T2DM) without Increasing Hypoglycemia Risk

Toujeo-1, a prospective observational study, investigates the effects of initiating BOT with Gla-300 in insulin-naïve pts with T2DM in Germany (n=1,680) and Switzerland, insufficiently controlled (A1c 7.5-10%) on oral antidiabetic drugs (OADs) in daily clinical practice. Primary endpoint (EP) is the proportion of pts achieving individualized A1c targets after 6 and 12 months, respectively. Secondary EPs include changes in A1c, fasting plasma glucose (FPG), body weight (BW) and insulin dose, hypoglycemia incidence and safety. Here we report results of pts recruited at German sites with 12 months results available (n=674). Pts baseline characteristics, efficacy and hypoglycemia EPs are shown in Table 1. Main OAD treatments were metformin ± DPP-4 inhibitors (49.4%). Twelve months after initiating Gla-300 therapy, proportions of pts at target were 48.4% (A1c at individual target), 30.5% (FPG ≤110 mg/dL), and 60.3% (A1c or FPG at target), respectively. Hypoglycemia rates were low (≤0.events/patient year) and no severe (nocturnal) hypoglycemia was reported. BW remained stable. In conclusion, initiating BOT with Gla-300 allowed insulin-naïve, uncontrolled T2DM pts to reduce their A1c by 1.20% w/o increasing hypoglycemia risk, especially w/o increase in severe (nocturnal) hypoglycemia. Disclosure M. Pfohl: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Sanofi. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Anderten: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp., Eli Lilly and Company, Boehringer Ingelheim GmbH, Pfizer Inc., AstraZeneca, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Takeda. K. Pegelow: Employee; Self; Sanofi-Aventis Deutschland GmbH. S. Pscherer: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. J. Seufert: Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH, GI Dynamics Inc.. Research Support; Self; GI Dynamics Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Ipsen Biopharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation. Research Support; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. Research Support; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi. Research Support; Self; Ypsomed AG.

Impact of patient and treatment characteristics on glycemic control and hypoglycemia in patients with type 2 diabetes initiated to insulin glargine or NPH: A post hoc, pooled, patient-level analysis of 6 randomized controlled trials.

The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine). Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed. Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: -1.32 ± 1.2% vs NPH: -1.26 ± 1.2%; P = 0.15), with greater reduction in the BMI ≥30 kg/m group than in the BMI <30 kg/m group. Glargine reduced A1C significantly more than NPH in the BMI <30 kg/m group (-1.30 ± 1.18% vs -1.14 ± 1.22, respectively; P = 0.008), but not in the BMI ≥ 30 kg/m group (-1.37 ± 1.19 vs -1.48 ± 1.22, respectively; P = 0.18). Similar proportions of patients achieved A1C target of <7% (glargine 30.6%, NPH 29.1%; P = 0.39). Incidence of severe and severe nocturnal hypoglycemia was significantly lower in glargine versus NPH-treated patients (2.0% vs 3.9%; P = 0.04, and 0.7% vs 2.1%; P = 0.002, respectively), and occurred primarily in the BMI <30 kg/m group. Initiation of basal insulin is highly effective in lowering A1C after oral antidiabetic agent failure. Glargine decreases A1C more than NPH in nonobese patients, and reduces the risk for severe and severe nocturnal hypoglycemia versus NPH both in obese and nonobese patients, but more so in nonobese patients. Thus, it is the nonobese patients who may benefit more from initiation of basal insulin as glargine than NPH.

Controversy about the relationship between sulfonylurea use and cardiovascular events and mortality.

Among a number of classes of oral antihyperglycemic drugs, sulfonylureas (SUs) demonstrating the potential effect to reduce blood glucose level have been used in a majority of patients with type 2 diabetes for many years. The pathophysiological processes by which SUs adversely induce the risk of cardiovascular disease have not been fully clarified. We summarized about the relationship between SU use and cardiovascular events and mortality in patients with type 2 diabetes.

Dead in bed syndrome: Mystery and fear

AbstractDead in bed (DIB) syndrome is a poorly understood cause of sudden and mysterious death in young people with type 1 diabetes on insulin therapy. Severe nocturnal hypoglycemia with unawareness is the most plausible mechanism which precipitates fatal arrhythmia in the vulnerable individual. Avoiding recurrent hypoglycemic episodes; screening for proarrhythmic condition in high-risk people with positive family history; and using real-time continuous glucose monitoring device in those with nighttime hypoglycemia and hypoglycemia unawareness can help to reduce the incidence of this deadly condition.

Gender-based differences in glycaemic control and hypoglycaemia prevalence in patients with type 2 diabetes: results from patient-level pooled data of six randomized controlled trials.

AimsTo determine the impact of gender on glycaemic control and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2DM).MethodsData were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin‐naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24–36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded.ResultsFor both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (−1.36 vs. −1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio (OR) 1.80; 95% confidence interval (CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia (OR: 3.80; 95% CI 1.72, 8.42; p = 0.001).ConclusionsThese observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk.

New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1).

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A1c (HbA1c) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m(2), and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.

Journal of Diabetes News

Journal of Diabetes News

Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial

Hypoglycaemia caused by glucose-lowering therapy has been linked to cardiovascular (CV) events. The ORIGIN trial provides an opportunity to further assess this relationship. A total of 12 537 participants with dysglycaemia and high CV-risk were randomized to basal insulin glargine titrated to a fasting glucose of ≤ 5.3 mmol/L (95 mg/dL) or standard glycaemic care. Non-severe hypoglycaemia was defined as symptoms confirmed by glucose ≤ 54 mg/dL and severe hypoglycaemia as a requirement for assistance or glucose ≤ 36 mg/dL. Outcomes were: (i) the composite of CV death, non-fatal myocardial infarction or stroke; (ii) mortality; (iii) CV mortality; and (iv) arrhythmic death. Hazards were estimated before and after adjustment for a hypoglycaemia propensity score. During a median of 6.2 years (IQR: 5.8-6.7), non-severe hypoglycaemic episodes occurred in 41.7 and 14.4% glargine and standard group participants, respectively, while severe episodes occurred in 5.7 and 1.8%, respectively. Non-severe hypoglycaemia was not associated with any outcome following adjustment. Conversely, severe hypoglycaemia was associated with a greater risk for the primary outcome (HR: 1.58; 95% CI: 1.24-2.02, P < 0.001), mortality (HR: 1.74; 95% CI: 1.39-2.19, P < 0.001), CV death (HR: 1.71; 95% CI: 1.27-2.30, P < 0.001) and arrhythmic death (HR: 1.77; 95% CI: 1.17-2.67, P = 0.007). Similar findings were noted for severe nocturnal hypoglycaemia for the primary outcome and mortality. The severe hypoglycaemia hazard for all four outcomes was higher with standard care than with insulin glargine. Severe hypoglycaemia is associated with an increased risk for CV outcomes in people at high CV risk and dysglycaemia. Although allocation to insulin glargine vs. standard care was associated with an increased risk of severe and non-severe hypoglycaemia, the relative risk of CV outcomes with hypoglycaemia was lower with insulin glargine-based glucose-lowering therapy than with the standard glycaemic control. Trial Registration (ORIGIN ClinicalTrials.gov number NCT00069784).

Impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes treated with insulin glargine or NPH insulin

To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin. A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated. Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration. There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Do high fasting glucose levels suggest nocturnal hypoglycaemia? The Somogyi effect-more fiction than fact?

The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l). Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia.

Impacto económico y sanitario de las hipoglucemias nocturnas asociadas al tratamiento de la diabetes mellitus tipo 2 con insulina glargina o insulina NPH

ObjectiveTo estimate the health and economic impact in Spain of nocturnal hypoglycemia linked to the treatment of type2 diabetes with insulin glargine (IG) or NPH insulin, both administered before bedtime. MethodsThe current cost of severe and symptomatic nocturnal hypoglycemia and the savings for the National Health Service (NHS) as a result of the reduction in the rate of occurrence of nocturnal hypoglycemia was calculated in the hypothetical case that the treatment with NPH was partially replace by IG. The use of health resources in clinical practice and the annual cost of hypoglycemic events were estimated by an expert panel of primary care and hospital clinicians. The reduction in the rate of hypoglycemic events with IG versus NPH was obtained from a published meta-analysis. ResultsThe annual cost of hypoglycemia was estimated at 1,121.98€ (518.90-1,990.19€) in the case of severe hypoglycemia, 473.85€ (243.22-733.82€) in case of symptomatic hypoglycemia with plasma glucose levels <36mg/dl, and 295.83€ (149.63-406.59€) with levels <70mg/dl. For an estimated replacement of NPH by IG of 4%, 7%, 10%, and 11% in four years, in Spain 6,772 hypoglycemic events would be avoided (487, 756, and 5,529, respectively, depending on its severity). The savings for the NHS would correspond to 1.6 million€ (ranging from €829,000 to 2.5 million€). ConclusionsThe treatment of diabetes type2 with IG (vs. NPH), both administered at bedtime, could reduce the rate of nocturnal hypoglycemia and the associated costs for the NHS.

New insulins and insulin therapy

New insulins and insulin therapy

Nocturnal Hypoglycemia Identified by a Continuous Glucose Monitoring System in Patients with Primary Adrenal Insufficiency (Addison's Disease)

Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days. In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.

Research progress of dead-in-bed syndrome in type 1 diabetes

Dead-in-bed syndrome (DBS) is a rare but devastating sudden death condition that mainly affects young patients with type 1 diabetes.Its mechanism is quite complicated and may involve multiple factors.Acute onset of recurrent and severe nocturnal hypoglycemia,abnormal cardiac repolarization,genetic factors,and obstructive sleep apnea may all contribute to ventricular arrhythmias and even sudden death.The future research plans include elucidating and understanding the underlying mechanisms and triggers for DBS,developing a risk stratification system,using real-time continuous glucose monitoring system to detect severe nocturnal hypoglycemia,and initiating appropriate therapeutic interventions to uhimately prevent the tragedy. Key words: Dead-in bed syndrome; Diabetes mellitus, type 1 ; Sudden death; Mechanism

Recent Advances in the Prevention of Hypoglycemia in Type 1 Diabetes

Iatrogenic hypoglycemia is one of the chief barriers to optimal glycemic control in people with type 1 diabetes (T1D). As a common contributor to morbidity and mortality in T1D, severe hypoglycemia (SH) is also a major fear for people with T1D and their families. Consequently, fear of hypoglycemia and hypoglycemia-avoidant behaviors are predominant limiting factors in achieving euglycemia in people with T1D. Nocturnal SH and hypoglycemia unawareness are prevalent obstacles in the detection of hypoglycemia which further impair the prevention and treatment of SH. Various strategies and technologies have already been developed to help detect and prevent hypoglycemia, including improved patient education, frequent self-monitoring of blood glucose levels, the use of rapid-acting and basal insulin analogs, continuous subcutaneous insulin infusion therapy, exercise-related insulin modifications, and continuous glucose monitors. The efficacy of these methods is well established, but further advances are still needed. The purpose of this review is to describe these currently available methods and to emphasize recent progress related to the prevention of hypoglycemia in T1D.

Switching to Biphasic Insulin Aspart 30 in Patients Uncontrolled on Human Premix Insulin

Two cases relating to switching from biphasic human insulin 30 (BHI 30) to biphasic insulin aspart 30 (BIAsp 30) are described. Case 1: switching from BHI 30 to BIAsp 30 due to inadequate glycosylated haemoglobin (HbA1c) control. Case 2: switching from BHI to BIAsp 30 due to nocturnal hypoglycaemia. Case 1: HbA1cfell from 7.9 % with BHI to 6.9 % with BIAsp 30 at the six-month follow-up. Postprandial glucose (PPG) fell from 12.6 mmol/l with BHI to 9.1 mmol/l with BIAsp 30. Case 2: a man who had experienced recurrent nocturnal hypoglycaemia with neutral protamine Hagedorn (NPH) or BHI was able to maintain his glycaemic control without severe nocturnal hypoglycaemia with BIAsp 30. BIAsp 30 offers advantages over BHI 30 in terms of faster absorption, higher peak concentrations, and a more rapid and pronounced prandial glucose-lowering effect, which means that BIAsp 30 can improve PPG control and reduce the risk of nocturnal and major hypoglycaemic episodes.

Specific features of pregnancy in patients with type 1 diabetes in the prepubertal period. Results of a 15-year long clinical observation

Aim. To evaluate effect of different factors on pregnancy course in patients with type 1 diabetes mellitus developing in the prepubertal period. Materials and methods. The study based at Endocrinological Research Centre included 77 women with prepubertal diabetes 18 of whom developedpregnancy that ended in delivery. Results. As per 2009, the age of the patients is 26,6?4,6 years. They became pregnant at 23,2?3,3 years and had had diabetes since the age of9,6?4,8 years. Their HbA1c level before and after pregnancy was 8,6?1,4 and 6,8?1,6% respectively, the difference being insignificant (p=0,3).Significant difference was documented between these HbA1c levels and that during pregnancy (p=0,0004 and 0.003 respectively). Nine (56,2%) patientsused ultrashort-acting insulin analogs and the remaining 7 (43,7%) recombinant human insulins. The mean insulin dose was 43,7?11 U/din the 1st trimester, 51,8?13,7 U/d in the 2bd trimester, and 45,3?10,8 U/d after delivery. 16 (88%) of the patients reported frequent hypoglycemia,five (27,8%) of them had episodes of severe daytime and nocturnal hypoglycemia. 11 (61%) developed microvascular diabetic complications beforepregnancy, with 9 (50%) having DR and 4 (22,2%) DN (microalbuminuria). The delivery occurred on weeks 36-37 in 7 (38,9%) women. Naturaland cesarean section deliveries took place in one and 17 (94,4%) patients respectively. Conclusion. Long-term follow-up of patients wit DM1 in accordance with algorithms of specialized medical aid to DM1 patients in Russia at a multidisciplinaryendocrinological centre decreases the risk of pregnancy and delivery complications and that of microvascular diabetic complications