Significant advancements have been made in diagnostic methods for early-stage diabetic polyneuropathy. Early and accurate diagnosis of diabetic polyneuropathy is crucial for preventing further complications and enabling timely intervention. Furthermore, there is a need for an objective numerical value to evaluate the early stage of diabetic polyneuropathy.
This study aimed to assess if patients can be divided into different strata, and to explore if these correspond to the risk of diabetic foot complications.
A set of 28 demographic, vascular, neurological and biomechanical measures from 2,284 (1,310 men, 974 women) patients were included in this study. A two-step cluster analysis technique was utilised to divide the patients into groups, each with similar characteristics.
Only two distinct groups: group 1 (n = 1,199; 669 men, 530 women) and group 2 (n = 1,072; 636 men, 436 women) were identified. From continuous variables, the most important predictors of grouping were: ankle vibration perception threshold (16.9 ± 4.1 V vs 31.9 ± 7.4 V); hallux vibration perception threshold (16.1 ± 4.7 V vs 33.1 ± 7.9 V); knee vibration perception threshold (18.2 ± 5.1 V vs 30.1 ± 6.5 V); average temperature sensation threshold to cold (29.2 ± 1.1°C vs 26.7 ± 0.7°C) and hot (35.4 ± 1.8°C vs 39.5 ± 1.0°C) stimuli, and average temperature tolerance threshold to hot stimuli at the foot (43.4 ± 0.9°C vs 46.6 ± 1.3°C). From categorical variables, only impaired sensation to touch was found to have importance at the highest levels: 87.4% of those with normal sensation were in group 1; whereas group 2 comprised 95.1%, 99.3% and 90.5% of those with decreased, highly-decreased and absent sensation to touch, respectively. In addition, neuropathy (monofilament) was a moderately important predictor (importance level 0.52) of grouping with 26.2% of participants with neuropathy in group 1 versus 73.5% of participants with neuropathy in group 2. Ulceration during follow up was almost fivefold higher in group 2 versus group 1.
Impaired sensations to temperature, vibration and touch were shown to be the strongest factors in stratifying patients into two groups with one group having almost 5-fold risk of future foot ulceration compared to the other.
A century has elapsed since the first formulated insulin made a debut. Progressive techniques and materials have overcome many problems of insulin therapy, including impurities, duration of action, antibodies against porcine or bovine insulin, and the expense of production1.
Despite the advances in oral antidiabetic drugs (OADs), insulin injection remains the keystone therapy in type 1 diabetes, type 2 diabetes with significantly impaired renal function, pregnant women, pancreoprivic diabetes, hospitalized patients, and those who cannot take oral pills. According to the American Diabetes Association, the early initiation of insulin therapy is recommended in the presence of ongoing catabolism (weight loss), symptoms of hyperglycemia, or when the A1c levels are >10% (86 mmol/mol) or blood glucose levels are ≥300 mg/dL (16.7 mmol/L)2. Moreover, insulin therapy always plays a role in the treatment for individuals who suffer treatment failure with oral antidiabetic drugs. As type 2 diabetes is a progressive disease, a significant number of individuals will ultimately need a daily injection of insulin as a result of declining pancreatic beta-cell function. For example, a nationwide cohort study revealed that adolescents with type 2 diabetes mellitus progressively required more intensive treatment after 1 year on oral antidiabetic drugs, with the majority eventually needing insulin therapy3. A significant subset of people with adult diabetes exhibit a combination of traits seen in both type 1 and type 2 diabetes. They are recognized as having a slowly progressive autoimmune form of diabetes, yet they do not initially require insulin upon diagnosis. These individuals are classified as having adult latent autoimmune diabetes, constituting approximately 2–12% of all cases of diabetes4.
Intermediate-acting and long-acting insulin are used as basal insulin, which is usually the beginning of insulin therapy. Common available insulin products are listed in Table 1. Insulin glargine and insulin degludec are deemed to be the most useful basal insulin currently. The DEVOTE Trial (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events) was the first study to compare the cardiovascular safety of insulin degludec with insulin glargine U100 in patients with type 2 diabetes at high risk of cardiovascular events. Both insulins demonstrated comparable efficacy in the cardiovascular events outcome (hazard ratio 0.91; 95% CI 0.78–1.06). Degludec exhibited significantly reduced occurrences of severe hypoglycemia and nocturnal severe hypoglycemia (with rate ratios of 0.60; 95% CI 0.48–0.76 and 0.47; 95% CI 0.31–0.73, respectively)5. Another study assessing the effectiveness and safety of insulin glargine U300 and insulin degludec in managing glyc
Very few cohort studies are available about the relation between remnant cholesterol (RC) and diabetes. Based on a prospective cohort survey, this research aimed at investigating if high RC was related to a future diabetes risk in the Chinese population, as well as to compare the association between RC, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C), and future diabetes risk.
6,700 baseline normoglycemic participants of the REACTION study's Beijing center were recruited in 2011–2012 and followed up in 2015. Multivariate Cox regression analyses were performed to explore the relationship of RC, HDL-C, LDL-C, TC, TG, LDL-C/HDL-C, TG/HDL-C, TC/HDL-C, and non-HDL-C and a future diabetes risk.
After potential confounders were adjusted for, only RC (HR 1.134, 95% CI 1.016–1.267, P = 0.025) was positively related to a future diabetes risk, and only HDL-C (HR 0.728, 95% CI 0.578–0.918, P = 0.007) was negatively related to a future diabetes risk. The rest of the lipid parameters were not related to a future risk of diabetes. Sensitivity and stratification analyses revealed that the relation between RC and future diabetes risk was stable. RC and future diabetes risk were still positively correlated even when the HDL-C was ≥1.04 mmol/L (HR 1.167, 95% CI 1.050–1.297, P = 0.004).
It was RC, but not other lipid parameters, that was independently and positively related to a future risk of diabetes among the Chinese general population. Moreover, the relationship between RC and diabetes risk was stable, even with appropriate levels of HDL-C.
This historical cohort study sought to research the relationship between eating behaviors and the incidence of type 2 diabetes in a large, long-term cohort of Japanese subjects.
Panasonic Corporation employees who had no history of diabetes and attended yearly health surveys between 2008 and 2018 were included in this study. The main outcome measure was diabetes onset.
This study included 128,594 participants and 6,729 participants who developed type 2 diabetes in the study period. Skipping breakfast, fast eating, snacking after dinner, and eating meals before sleeping were linked with the risk of the incidence of type 2 diabetes. In individuals with a BMI < 25 kg/m2, fast eating (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.37–1.90), and eating meals before sleeping (HR: 1.09, 95% CI: 1.02–1.17) were likewise associated with an increased risk of incident type 2 diabetes. Nevertheless, fast eating (HR: 1.08, 95% CI: 0.89–1.30) and meals before sleeping (HR: 0.94, 95% CI: 0.88–1.01) were not related to the occurrence of type 2 diabetes in individuals with a BMI ≥25 kg/m2 (P value for interaction = 0.0007 [fast eating] and 0.007 [meals before sleeping], respectively). No significant interaction effect between sex and eating behavior was found.
With respect to Japanese people, especially in people with a BMI < 25 kg/m2, eating behaviors may be a risk factor for the occurrence of type 2 diabetes.
To date, a considerable number of studies have shown the involvement of human gut microbiota in the development and progression of various kinds of diseases, including metabolic and neurological disorders. Fecal microbiota transplantation (FMT), the process of transplanting gut microbiota of healthy donors into intestines of patients, is considered a comprehensive therapy to improve enteric environments. FMT has been shown to suppress the progression of type 1 diabetes mellitus1 and restore insulin sensitivity in type 2 diabetes mellitus2 patients in randomized control trials (RCT). These findings indicate critical roles of gut microbiota dysbiosis in insulin deficiency and resistance. In addition, animal and preliminary human studies imply that FMT can be a potential therapy for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis.
Diabetic peripheral neuropathy (DPN) is the most frequent and early-onset chronic complication of diabetes mellitus. Although DPN shows a variety of nerve injury patterns, its major form is distal symmetric polyneuropathy (DSPN). Ultrastructural studies have shown that the main pathology of DSPN is axonal degeneration of myelinated and unmyelinated fibers, which might characterize the disease as both metabolic and neurodegenerative disorders. As the etiology and onset mechanisms of DSPN remain largely unclear, no disease-modifying therapies against it are currently available. A recent study by Yang et al.3 shed light on gut microbiota dysbiosis as a novel pathogenic factor of DSPN; the details are described in the following paragraphs.
In the first study, fecal microbiota from individuals with normal glucose levels, patients with diabetes mellitus but not DSPN and patients with DSPN (M-DSPN) were transplanted into genetically diabetic db/db mice. M-DSPN induced more severe neurological manifestations (reduced nociception and nerve conduction velocities) and histopathology (reduced intraepidermal nerve fiber density and downregulated expression of 200-kD neurofilament, myelin basic protein, and brain-derived neurotrophic factor in spinal sensory ganglia and sciatic nerves) than microbiota from individuals with normal glucose levels or patients with diabetes mellitus but not DSPN. In addition, the M-DSPN-treated group of mice showed more severe gut barrier dysfunction (reduced expression of tight junction proteins in colon tissue, and increased fluorescent dextran permeability) and systemic inflammation (increased plasma levels of lipopolysaccharide-binding protein, tumor necrosis factor-α and interleukin-6) than the other groups. Lipopolysaccharide-binding protein can bind to antigens produced by bacteria, thereby being considered a marker of bacterial antigen load in the blood. Consistent with the mouse phenotypes, genomic and metabolomic analyses with the gut micr
The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus.
The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet β-cell function, insulin resistance and comprehensive management measures.
Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0–4.0 years). The baseline HbA1c was 11.2% (IQR 9.2–12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3–6.1%]) in the half-year course group and the highest in the 4-year course group (9.0 [IQR 6.8%–11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of β-cell function, and a lower proportion with a controlled diet, moderate-intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of β-cell function at follow up, continuous moderate-intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control.
Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet β-cell function. A good lifestyle, especially moderate-intensity exercise, can help such cases better control their blood glucose level.
Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti-oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes-related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model.
To induce insulin resistance, mice were fed a high-fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose-regulated protein 78, phosphodiesterase type 5, protein kinase R-like endoplasmic reticulum (ER) kinase, and phospho-protein kinase R-like endoplasmic reticulum kinase in heart tissue.
The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate-specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high-fat diet-induced cardiac dysfunction and decreased ER stress.
PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.
Shimada A, Kawasaki E, Abiru N, Awata T, Oikawa Y, Osawa H, Kajio H, Kozawa J, Takahashi K, Chujo D, Noso S, Fukui T, Miura J, Yasuda K, Yasuda H, Imagawa A, Ikegami H. New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes of the Japan Diabetes Society (English version). J Diabetes Investig. 2024 Feb;15:254–257.
In the original publication of the article, under the discussion section, in the following paragraph “Moreover, regarding the concept of …”, “for” should be replaced with “at” in the third point.
The correct sentence should read as follows “(3) insulin treatment required at more than 6 months after the diagnosis of diabetes.”
Similarly, under the same section, in the following paragraph “According to the IDS diagnostic criteria for…”, “for” should be replaced with “at” in a few occurrences.
The correct sentences should read as follows “According to the IDS diagnostic criteria for LADA, insulin treatment is required at more than 6 months [4] after the diagnosis of diabetes. However, considering the diagnostic criteria of AT1D [6], we described the necessity of insulin treatment at more than 3 months in the new criteria of SPIDDM (2023) and added a comment on the necessity of insulin treatment at more than 6 months after diagnosis of diabetes in typical cases.”
Finally, in Table 1, on third factor, “for” should be replaced with “at”. The correct sentence should read as follows “(3) Gradual reduction in insulin secretion overtime, requirement of insulin treatment at more than 3 monthsb after diagnosis of diabetes, and severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity <0.6 ng/mL) at the last observed time point”.
We apologize for this error.
To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan.
Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups.
Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively.
In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.
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