Volume 08 · Issue 01 · 2016

Diabetes and osteoporosis are two chronic diseases widely prevalent in China. diabetic osteoporosis (DOP) has become a common clinical problem that we must face. DOP refers to osteopenia, bone microstructure destruction and bone fragility increase in the pathophysiological process of diabetes, which is considered as one of the chronic complications of diabetes. Insufficient gain of peak bone mass, poor glycemic control, accumulation of advanced glycation end products (AGEs), insulin deficiency or insufficient action, and various chronic complications of diabetes may affect bone mass and bone mass in diabetic patients. Patients with type 1 diabetes mellitus (T1DM) usually have reduced bone mineral density; Patients with type 2 diabetes mellitus (T2DM) may not have low bone mass, but bone strength decreases, and at the same time diabetics have an increased risk of falling. Certain antidiabetic medications may have bone side effects. All the above factors can increase the occurrence of DOP and the risk of fracture. It is recommended to carry out osteoporosis screening and fracture risk assessment in diabetic patients, and give comprehensive intervention measures to high-risk patients as early as possible.

Diabetes mellitus is a chronic metabolic disease with high morbidity and mortality. Osteoporosis is a metabolic bone disease characterized by reduced bone strength and increased risk of fracture. The prevalence of both diseases increased with age. Back in 1927, Morrison and Began^[1]Delayed bone development and bone atrophy have been reported in children with long-term diabetes mellitus. In 1947, Reifenstein and Albright^[2]Bone loss and osteoporosis were reported for the first time in a diabetic child with poor glycemic control. 1952, Berney^[3]This paper expounds the coexistence of diabetes and osteoporosis and the relationship between them, and then unveils the prelude to the study of whether osteoporosis is one of the chronic complications of diabetes. This article will elaborate the relationship between type 1 diabetes mellitus (TIDM) and type 2 diabetes mellitus (T2DM) and osteoporosis, respectively.

Diabetes is widely prevalent all over the world, and the related complications are very harmful. Skeletal complications are also an important part of it, such as Charcot osteoarthritis. Osteoporosis is the most common bone disease in middle-aged and elderly people, and the fracture caused by it is also one of the main causes of disability and death. Osteoporosis is also the most important metabolic bone disease in diabetic patients. Type 1 diabetes mellitus (T1DM) has long been recognized for bone damage. Patients with this type have reduced bone mineral density and significantly increased fracture risk. However, the effects on bone in patients with type 2 diabetes mellitus (T2DM) are controversial. However, with the accumulation of research evidence, both T1DM and T2DM have been regarded as risk factors for osteoporosis, such as the 2014 edition of the guidelines of the National Osteoporosis Foundation of the United States^[1]。 This article will discuss the impact of diabetes on osteoporosis and its mechanisms.

In the past 10 years, people have more and more clearly recognized that bone is an endocrine organ, which plays an important role in regulating energy metabolism in the whole body. Based on the results of basic and clinical studies, this paper introduces the regulatory effect of bone on sugar metabolism.

To investigate the association between sleep disorder and osteoporosis in elderly female patients with type 2 diabetes.

Five hundred and thirty-six elderly female patients with type 2 diabetes aged above 60 years were recruited from July 2011 to July 2014. They were divided into two groups according to Pittsburgh Sleep Quality Index: patients without sleep disorder and patients with sleep disorder. The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines(L2-L4) was measured by dual-energy X-ray absorptiometry. The groups were further divided into osteoporosis negative group and osteoporosis group. Biochemical indicators were detected in the two groups. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed. We compared the differences of bone mineral density as well as α-cell and β-cell function after fasting and glucose-load. The Logistic regression analysis was performed to analyze sleep disorder as well as osteoporosis and other indicators.

(1)The bone mineral density of femoral neck, Wards triangle, greater trochanter and lumbar spines(L2-L4) was significantly lower(t=2.9652-6.3403, all P<0.05) and the prevalence of osteoporosis was significantly higher in patients with sleep disorder compared to those in patients without sleep disorder(χ²=13.891, P<0.05). Bone mineral density of sleep disorder subgroup was lower than those without sleep disorder, especially for greater trochanter and lumbar spines(L2-L3). (2) The level of glucagon at each time point and area under curve of glucagon as well as 0, 30, 180 min glucagon/insulin ratio and 0, 30, 60, 180 min glucagon/glucose ratio were significantly higher in patients with sleep disorder than those in patients without(t=1.0332-19.6437, all P<0.05). The levels of glycated hemoglobin A1c(HbA_1c), fructosamine, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) were significantly higher in patients with sleep disorder compared to those without sleep disorder ((8.0%±1.9%) vs (7.3%±1.6%), (0.32±0.10) vs (0.30±0.08)mmol/L, (13±4) vs (12±4)mU/L, (4.7±0.8) vs(3.8±0.8), t=4.5956, 2.5445, 2.9871, 11.8356, all P<0.05). Insulin sensitivity index was lower in patients with sleep disorder than that in patients without sleep disorder (-4.2±0.5 vs -4.0±0.4,t=4.1559, P<0.05). Significant changes of the above indicators were observed in sleep disorder subgroup compared to those without sleep disorder(allP< 0.05). (3) Logistic regression analysis showed that sleep disorder was positively related to HOMA-IR, HbA_1c and area under curve of glucagon (OR=2.452, 1.119, 1.223, all P<0.05), whereas osteoporosis was positively related to postmenopausal duration, HbA_1c, area under curve of glucagon and sleep disorder(OR= 20.677, 19.948, 23.445, 23.682, all P<0.05).

Sleep disorder may be associated with osteoporosis via influencing islet α-cell and β-cell functions in elderly female patients with type 2 diabetes.

To investigate the effects of metformin on bone mineral density (BMD), the expression of bone morphogenetic protein 2 (BMP2) and Toll-like receptor 4 (TLR-4)/nuclear factor κappa B(NF-κB) in diabetic rats.

Sixty 4-5 weeks-old male Sprague-Dawlry (SD) rats were divided into normal control group (NC group, n=15) and experimental group (n=45). The experimental group was fed with high-sugar high-fat diet. Then a small dose of streptozotocin was injected intraperitoneally. According to random number table, the rats were divided into diabetes group(DM group, n=16) and diabetes +metformin group(DM+ MET group, n=15). The DM+ MET rats were treated with metformin for 16 weeks by gavage(900 mg/(kg·d)), while rats in other groups were treated with saline by gavage. The BMD of different parts in the rats and body composition was obtained with double energy X array(DEXA) scan. The expression of osteocalcin(OCN) in the rats was measured with enzyme linked immunosorbent assay(ELISA). Protein expression of TLR-4, NF-κB, and BMP-2 was determined with Western blot. mRNA expression of TLR-4 and NF-κB was determined with RT-PCR. Differences among three groups were assessed by one-way analysis of variance.

Compared with NC group, the BMD of upper limbs and whole body in DM group was decreased(P<0.05); The levels of alkaline phosphatase(ALP) and OCN were decreased ((130±39) vs (62±14) U/L; (2.84±0.52) vs (1.94±0.13) μg/g,t=3.273, 3.367, both P<0.05); The levels of TLR-4 and NF-κB were increased (bothP<0.05); but the values of BMP-2 was decreased (P<0.05). There was no significant difference in BMD, OCN and ALP expression between DM group and DM+MET group (P>0.05). Compared to the DM group, the levels of TLR-4 and NF-κB of the DM+ MET group were lower (bothP< 0.05). And the values of BMP-2 was higher (0.23 ± 0.05 vs 0.35 ± 0.08,t=4.098, P<0.05).

Metformin may inhibit TLR-4/NF-κB expression and increase BMP-2 expression. But it has no significant impact on the BMD of thigh, torso, spine and body in the diabetic rats during the treatment period (16 weeks).

To compare the Diabetes Attitudes, Wishes and Needs second study (DAWN2) results between China and other countries.

In the year of 2012, a total of 504 Chinese patients with diabetes and 8 092 patients with diabetes from other countries were surveyed with questionnaires via online, telephone or in person methods. The survey was related to quality of life, psychological well-being, self-management, empowerment and health care support. The value was estimated with generalized linear mixed models and compared with t test.

As evaluated by Problem Areas in Diabetes Scale 5 (PAID-5), the composite score for Chinese patients with diabetes(37.6) was statistically significantly higher than the average level of other countries(33.7)(t=-3.37, P<0.001); incidence of diabetes related distress was reported by 47.3% in Chinese patients with diabetes, and it was significantly higher than that in other countries(41.3%)(t=-2.58, P=0.010). As evaluated by Diabetes Empowerment Scale-Short Form (DES-SF), the composite score in Chinese patients (47.3) was significantly higher than that in patients from other countries(37.6) (t=- 8.89, P<0.001). As evaluated by the Summary of Diabetes Self-Care Activities (SDSCA), in the past 7 days, Chinese patients performed " foot check" for an average of 2.9 days, which was significantly lower than that in patients from other countries(3.6 days) (t=5.29, P<0.001). As evaluated by Patient Assessment of Chronic Illness Care(PACIC), the composite score in Chinese patients was 42.4 and it was significantly higher than that in patients from other countries(36.5) (t=- 4.99, P<0.001). However, the rate of patients reporting ' I was satisfied that my care was well-organized' was 25.6% in Chinese patients and it was significantly lower than that in other countries(52.4% ) (t=10.25, P<0.001).

Diabetes is apparently a physical and psychological burden to Chinese patients. Chinese patients with diabetes are empowered well. The health care support should be improved and special attention should be paid to mental health and foot care those patients.

To investigate the efficacy and safety of liraglutide versus sitagliptin in obese patients with inadequately controlled type 2 diabetes with insulin therapy.

Ninety-eight cases of type 2 diabetic with body mass index(BMI)>25 kg/m², waist circumference(male>90 cm and female> 85 cm), glycated hemoglobin A_1c(HbA_1c) 7.5%-9.5% were enrolled from February 2013 to February 2014 in Quanzhou First Hospital Affiliated to Fujian Medical University. All subjects who received metformin (at least 1 000 mg/d) and insulin (at least 45 U/d) for at least 6 months were numberally randomly assigned to receive additional liraglutide (0.6 mg for one week followed by 1.2 mg later) once a day (n=48) or sitagliptin 100 mg once a day(n=50) in a 16-week study. Participants were evaluated for glycaemic control, weight, blood pressure, lipid profiles, and adverse events at baseline and 16 weeks. Paired t test was used to analyze changes within groups. Two-sample t test was applied to compare differences of continuous variables between groups. Rates were compared by using the Chi-Square test.

Compared to the baseline, after 16-week treatment, the HbA_1c decreased for 1.4%±0.4% in liraglutide group and for 1.2%±0.4% in sitagliptin group(t=2.5, P<0.05). The proportion of patients whose HbA_1c reached the target of less than 7.0% was 53.7% and 37.2% in the liraglutide group and sitagliptin group, respectively(χ²=2.3, P>0.05). After 16-week treatment, weight loss for (2.5±2.4) kg was observed in the liraglutide group, while weight gain was reported in the sitagliptin group for (0.3±1.2) kg(t=6.8, P<0.01). After 16-week treatment, systolic blood pressure in the liraglutide group reduced for (7.3±6.5) mmHg and for (1.7±3.7) mmHg in sitagliptin group(t= 4.8, P<0.01). The improvement of lipid profile, homocysteic acid and diastolic blood pressure after the treatment were all statistically significant in the two groups (allP<0.05), but there was no significant difference in change values of those indexes between the two groups (allP>0.05). The incidence of gastrointestinal adverse events was greater in the liraglutide group than that in sitagliptin group.

Liraglutide and sitagliptin applied to patients with inadequately glycemic controlled and obese type 2 diabetes with insulin therapy can beneficial to regulate glucose. Liraglutide is superior on glucose control and drop of weight and systolic blood pressure to sitagliptin. Stagliptin leads to fewer gastrointestinal effects than liraglutide.

To identify the cause and its pathogenic mechanism in one case with permanent neonatal diabetes mellitus(PNDM).

One case of PNDM diagnosed in Peking Union Medical College Hospital was analyzed for clinical features. Genomic DNA was extracted, followed by amplification with polymerase chain reaction and direct sequencing of glucokinase (GCK) gene. Wild and mutant plasmids were constructed and then expressed in E.coli. The recombinant proteins were purified, then tested to clarify their enzyme kinetics and thermal stability. Data between two groups were analyzed by t test.

Compound heterozygous mutation c.571 C>T(R191W) and c.1136 C>A(A379E) in GCK gene were detected in this child. Compared with the wild type, mutants R191W and A379E had lower protein yield ((86±9) vs (48±8) mg/L;(86±9) vs (54±5) mg/L;t=5.56, 5.36, both P<0.01), lower appetency for glucose(the half-saturating substrate concentration (S_0.5) for glucose:(7.63±0.21) vs (35.27±2.20)mmol/L; (7.63±0.21) vs (13.30±0.44)mmol/L, t=-21.70, -20.32, both P<0.01), lower appetency for ATP(K_m: (0.30±0.01) vs (0.42± 0.01) mmol/L; (0.30±0.01) vs (0.54±0.04) mmol/L, t=-17.02,-10.68, both P<0.01) and lower catalytic ability ((20.9±2.1)/s vs (6.5 ± 1.0)/s; (20.9±2.1)/s vs (10.5 ± 1.1)/s;t=10.61, 7.58, both P<0.01). The both mutants also showed increased thermal instability.

Compound heterozygous mutations R191W and A379E in GCK gene promote the development of PNDM by affecting enzyme kinetics of glucokinase as well as lowering protein stability.

To observe the effect of telmisartan on the expression of nicotinamide adenine dinucleotide (NADPH)oxidase subunit p22phox and nuclear factor erythroid 2-related factor(NRF-2) in the testes of type 1 diabetic rats. To investigate the protective effect and mechanism of telmisartan on testicular tissue of type 1 diabetic rats.

Male SD rats were randomly divided into normal control (group NC,n=8),diabetes(group DM, n=8) and diabetes treated with telmisartan(DT,n=8). Diabetes was induced by a single intraperitoneal injection of streptozotocin. The rats in group DT were given telmisartan in dose of 10 mg/kg once a day by gavage. After telmisartan treatment for 8 weeks, blood samples were collected to detect the levels of biochemical index,insulin and testosterone. The expression of testicular NADPH oxidase subunit p22phox and p47phox, NRF-2, superoxide dismutase(SOD), quinine oxidoreductase1(NQO1) and heme oxygenase 1(HO-1) were assayed. One-way analysis of variance was used among multiple groups and t analysis was applied for comparison between two groups.

The levels of blood glucose, mRNA and protein expression of testicular p22phox were significantly increased in group DM than those in group NC (27.38±0.82 vs 5.11±0.23, 0.95±0.06 vs 0.78±0.12, 1.02±0.09 vs 0.59±0.19, t= 87.434,3.020, 4.610, all P<0.05).The levels of serum insulin, serum and testicular testosterone, testicular weight, sperm number and motility, the activity and mRNA expression of testicular SOD, and the mRNA and protein expression of testicular NRF-2, NQO1 and HO-1 were significantly decreased in group DM than those in group NC (t=2.180-29.396, all P<0.05). After telmisartan treatment for 8 weeks, the levels of blood glucose, the mRNA and protein expression of testicular p22phox were significantly decreased in group DT than those in group DM (t=20.940, 4.580, 2.860, all P<0.05). The levels of sperm number and motility, the activity and mRNA expression of testicular SOD,the mRNA and protein expression of testicular NRF-2, NQO1 and HO-1 were significantly increased in group DT than those in group DM (t=2.00-6.47, all P<0.05). There were no significant differences in serum insulin,serum and testicular testosterone, the expression of testicular NQO1 between group DM and group DT (allP>0.05). There was no significant difference in the expression of testicular p47phox among three groups (allP>0.05).

Telmisartan may play a protective role on testicular tissues in type 1 diabetic rats.

Insulin autoimmune syndrome (IAS), also known as autoimmune hypoglycemia, was developed in 1970 by Hirata, Japan^[1]It is reported for the first time that the main feature is the presence of high concentrations of immunoactive insulin and high titer insulin autoantibodies (IAA) in the blood without the use of exogenous insulin, causing spontaneous hypoglycemia. In 1985, China was established by Xiang Dazhen and others^[2]First reported, more than 80 cases of the disease have been reported by 2014^[3]。 A patient with IAS caused by pyrithiol hydrochloride was recently admitted to our hospital. After more than one year of treatment and follow-up, the treatment effect was good. The report is as follows.

Diabetic foot is one of the most serious diabetic complications. Its routine treatment requires multi-disciplinary cooperation, including blood sugar control, anti-infection, improvement of blood circulation, local debridement and dressing change, nerve nutrition, decompression, regular foot care and education, suitable footwear and socks protection, etc^[1]。 In addition, adjuvant therapy such as hyperbaric oxygen, negative pressure suction, new dressings and other treatment measures should also be considered^[2]。 Among them, hyperbaric oxygen therapy has been used as an adjuvant treatment for diabetic foot ulcer for 50 years^[3], it is a treatment modality that places the patient in an environment above absolute atmospheric pressure, breathes 100% oxygen for a short time, and delivers oxygen to hypoxic tissues through the respiratory tract and blood circulation to promote local ulcer healing. It has been reported that hyperbaric oxygen can increase the wound healing rate from 29% to 52%^[4], reducing the amputation rate from 30.07% to 13.63%^[5]。 This article will summarize the principles, indications, contraindications, side effects and clinical application of hyperbaric oxygen.

With the improvement of living standards and lifestyle changes, the incidence of metabolic syndrome (MS) in China is increasing year by year, accompanied by the increase of cardiovascular disease risk factors, which brings a heavy burden to society and economy. MS is a group of abnormal metabolic syndromes mainly caused by obesity and insulin resistance. Its components include obesity, type 2 diabetes mellitus (T2DM) or abnormal glucose tolerance, dyslipidemia, hypertension, non-alcoholic fatty liver disease, microalbuminuria, low-grade inflammatory reaction, abnormal blood coagulation and fibrinolytic system activity, polycystic ovary syndrome, etc. With the continuous addition of new diseases, it suggests that its essence is multi-faceted and complex, and many problems need to be clarified.

The concept of "dawn phenomenon" was first developed by Schmidt et al.^[1]First proposed and named. In a study to explore the relationship between 24-h blood glucose variability and insulin, they found that 10 of the 11 enrolled patients with type 1 diabetes experienced an increase in fasting blood glucose in the morning and affected postbreakfast blood glucose, Schmidt et al^[1]This phenomenon of significant morning blood sugar rise is named "dawn phenomenon". "Dawn phenomenon" refers to the occurrence of hyperglycemia or increased insulin requirements at dawn (about 4:00 to 8:00) in diabetic patients when their blood sugar is well controlled at night and there is no hypoglycemia^[1,2]。 It is generally recommended to define "dawn phenomenon" hyperglycemia as when plasma glucose levels are at least 10 mg/dl above the nighttime minimum or when insulin requirements increase by 20% above the nighttime minimum.