Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years

Brain ◽  
2021 ◽  
Author(s):  
Dan Ziegler ◽  
Gidon J Bönhof ◽  
Alexander Strom ◽  
Klaus Straßburger ◽  
Yanislava Karusheva ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Nerve Fibre ◽  
Lower Limbs ◽  
Nerve Fibres ◽  
Recent Onset ◽  
Onset Type ◽  
Large Fibre

Abstract It has been traditionally suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by a predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible. Participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 350/570) and age-matched glucose-tolerant control individuals (Control 1/Control 2: n = 114/190) were assessed by nerve conduction studies (NCS), thermal detection thresholds (TDT), vibration perception threshold (VPT), Neuropathy Symptom Score (NSS), Neuropathy Disability Score (NDS), and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1/type 2 diabetes: n = 102/226; Control 1/Control 2: n = 109/208). Subsets of participants with type 1/type 2 diabetes were followed for 5 years (n = 184/307; IENFD subset: n = 18/69). DSPN was defined by the Toronto Consensus criteria. At baseline, DSPN was present in 8.1 and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centile of the controls were IENFD (13.7%) and individual NCS (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar VPT (17.5%), and individual NCS (up to 11.8%) in those with type 2 diabetes, whereas TDT abnormalities did not differ between the control and diabetes groups. After 5 years in type 2 diabetes participants, the highest progression rates from the normal to the abnormal range were found for IENFD (18.8%) by -4.1 ± 2.8 fibres/mm, malleolar VPT (18.6%) by 9.1 ± 20.2 µm, and NDS (15.0%) by 3.7 ± 1.5 points, while vice versa the highest regression rates were observed for NDS (11.2%) by -3.1 ± 1.3 points, sural nerve amplitude (9.1%) by 4.7 ± 3.0 µV, IENFD (8.7%) by 1.4 ± 1.3 fibres/mm, and NSS (8.2%) by -5.8 ± 1.6 points. In type 1 diabetes participants, no major progression was seen after 5 years, but subclinical DSPN regressed in 10.3%. These findings point to an early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5 years peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.

1888-P: Impaired Insulin Clearance Relates to Increased Liver Fat Content in Recent-Onset Type 2 Diabetes and to Impaired Glucose Control in Recent-Onset Type 1 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1888-P
Author(s):  
SOFIA ANTONIOU ◽  
OANA P. ZAHARIA ◽  
KLAUS STRASSBURGER ◽  
YANISLAVA KARUSHEVA ◽  
KALMAN BODIS ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Glucose Control ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Recent Onset ◽  
Onset Type ◽  
Impaired Insulin

scholarly journals Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes

Diabetologia ◽  
2020 ◽  
Author(s):  
Dan Ziegler ◽  
◽  
Alexander Strom ◽  
Klaus Straßburger ◽  
Birgit Knebel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Plasma Lipid ◽  
Low Frequency ◽  
Recent Onset ◽  
Onset Type ◽  
Cardiac Autonomic Dysfunction ◽  
Lipid Metabolites

Abstract Aims/hypothesis Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes. Methods We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (n = 60) and type 2 diabetes (n = 95) after 5 years. Results In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (r = −0.242 to r = −0.349; p ≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered. Conclusions/interpretation Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes.

scholarly journals Early-Onset Type 2 Diabetes Misdiagnosed as Type 1 Diabetes in a 15-Year-Old Nigerian Girl: A Case Report

2020 ◽  
Vol 09 (04) ◽  
pp. 107-114
Author(s):  
Adeyemi Michael Olamoyegun ◽  
Oluwabukola Ayodele Ala ◽  
Olayinka Olomooba Saliu
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Case Report ◽  
Early Onset ◽  
Onset Type

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy

2021 ◽  
pp. 108023
Author(s):  
Timothy L. Middleton ◽  
Steven Chadban ◽  
Lynda Molyneaux ◽  
Mario D'Souza ◽  
Maria I. Constantino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Renal Replacement Therapy ◽  
Young Adult ◽  
Replacement Therapy ◽  
Adult Onset ◽  
Onset Type ◽  
Diabetes Progression

scholarly journals Diagnosis of neuropathy and risk factors for corneal nerve loss in type 1 and type 2 diabetes: A corneal confocal microscopy study

2020 ◽  
Author(s):  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
Ioannis N Petropoulos ◽  
Georgios Ponirakis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Peripheral Neuropathy ◽  
Nerve Fibre ◽  
Fibre Length ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

<b>Purpose: </b>To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss. <p><b>Methods: </b>490 participants including 72 healthy controls, 149 with type 1 diabetes and 269 with type 2 diabetes underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.</p> <p><b>Results: </b>Corneal nerve fibre density (CNFD) (P<0.0001, P<0.0001), branch density (CNBD) (P<0.0001, P<0.0001) and length (CNFL) (P<0.0001, P=0.02) were significantly lower in patients with type 1 and type 2 diabetes, compared to controls. CNFD (P<0.0001), CNBD (P<0.0001) and CNFL (P<0.0001) were lower in type 1 diabetes compared to type 2 diabetes. Receiver operating characteristics (ROC) curve analysis for the diagnosis of DPN demonstrated a good area under the curve (AUC) for CNFD=0.81, CNBD=0.74 and CNFL=0.73. Multivariable regression analysis showed a significant association between reduced corneal nerve fibre length with age (β=-0.27, P=0.007), HbA1c (β=-1.1, P=0.01) and weight (β=-0.14, P=0.03) in patients with type 2 diabetes and with duration of diabetes (β=-0.13, P=0.02), LDL cholesterol (β=1.8, P=0.04), and triglycerides (β=-2.87, P=0.009) in patients with type 1 diabetes. </p> <b>Conclusion: </b>CCM identifies more severe corneal nerve loss in patients with type 1 compared to type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fibre length differ between type 1 and type 2 diabetes.

scholarly journals Low-grade Inflammatory Marker Profile May Help to Differentiate Patients With LADA, Classic Adult-Onset Type 1 Diabetes, and Type 2 Diabetes

Diabetes Care ◽  
2018 ◽  
Vol 41 (4) ◽  
pp. 862-868 ◽  
Author(s):  
Esmeralda Castelblanco ◽  
Marta Hernández ◽  
Andrea Castelblanco ◽  
Mònica Gratacòs ◽  
Aureli Esquerda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Inflammatory Marker ◽  
Low Grade ◽  
Adult Onset ◽  
Onset Type ◽  
Marker Profile
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