Simple Quantitative Sensory Testing Reveals Paradoxical Co-existence of Hypoesthesia and Hyperalgesia in Diabetes

Background: Diabetic neuropathy is characterized by the paradoxical co-existence of hypo- and hyperalgesia to sensory stimuli. The literature shows consistently sensory differences between healthy and participants with diabetes. We hypothesized that due to differences in pathophysiology, advanced quantitative sensory testing (QST) might reveal sensory discrepancies between type 1 (T1D) and type 2 diabetes (T2D). Furthermore, we investigated whether vibration detection thresholds (VDT) were associated with sensory response. Method: Fifty-six adults with T1D [43 years (28–58)], 99 adults with T2D [65 years (57–71)], and 122 healthy individuals [51 years (34–64)] were included. VDT, pressure pain detection thresholds (pPDT) and tolerance (pPTT), tonic cold pain (hand-immersion in iced water), and central pain mechanisms (temporal summation and conditioned pain modulation) were tested and compared between T1D and T2D. VDT was categorized into normal ( 25 V). Results: In comparison to healthy, analysis adjusted for age, BMI, and gender revealed hypoalgesia to tibial (pPDT): p = 0.01, hyperalgesia to tonic cold pain: p < 0.01, and diminished temporal summation (arm: p < 0.01; abdomen: p < 0.01). In comparison to participants with T2D, participants with T1D were hypoalgesic to tibial pPDT: p < 0.01 and pPTT: p < 0.01, and lower VDT: p = 0.02. VDT was not associated with QST responses. Conclusion: Participants with T1D were more hypoalgesic to bone pPDT and pPTT independent of lower VDT, indicating neuronal health toward normalization. Improved understanding of differentiated sensory profiles in T1D and T2D may identify improved clinical endpoints in future trials

Poremećaji neurokognitivne funkcije, mentalnoga zdravlja i razine glukoze u zemljoradnika izloženih organofosfornim pesticidima

About 25 million agricultural workers in the developing world suffer from at least one episode of poisoningeach year, mainly by anticholinesterase-like organophosphates (OPs). The objective of this cross-sectional study was to establish the OP toxicity in 187 occupationally exposed farmers in terms of neurocognitive impairment, mental health status, clinical symptoms, diabetes, and haematological factors. The exposed group was compared to 187 healthy age-, sex-, and education-matching controls. Neurocognitive impairment was measured using the Subjective Neurocognition Inventory (SNI) and mental health status using the General Health Questionnaire-28 (GHQ-28). The subjects were also tested for fasting blood glucose (FBG), blood urea nitrogen (BUN), cholesterol (CL), triglycerides (TG), creatinine, oral glucose tolerance test (GTT), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The exposed farmers showed higher FBG (p<0.001), BUN (p=0.007), CL (p<0.001), oral GTT (p<0.001), and lower AST (p<0.001), ALP (p<0.001), and creatinine (p=0.004) than controls. The rates of anxiety/insomnia and severe depression were also significantly higher in the farmers than in controls (p=0.015 and p<0.001, respectively). Meanwhile, the rate of social dysfunction was signifi cantly lower than in controls (p<0.001). Disorders affecting psychomotor speed, selective attention, divided attention, verbal memory, nonverbal memory, prospective memory, spatial functioning, and initiative/energy were all lower in the farmers (p<0.001). Farmers showed clinical symptoms eczema, saliva secretion, fatigue, headache, sweating, abdominal pain, nausea, superior distal muscle weakness, inferior distal muscle weakness, inferior proximal muscle weakness, breath muscle weakness, hand tingling, foot tingling, epiphoria, polyuria, miosis, dyspnoea, bradycardia, and rhinorrhoea, which all signifi cantly correlated with the number of working years. These fi ndings indicate that farmers who work with OPs are prone to neuropsychological disorders and diabetes.Oko 25 milijuna zemljoradnika iz zemalja u razvoju imalo je barem jednu epizodu trovanja na godinu, uglavnom antikolinesteraznim organofosfatima. Cilj ovoga križnog ispitivanja bio je utvrditi u 187 profesionalno izloženih zemljoradnika toksično djelovanje organofosfata na neurokognitivnu funkciju, mentalno zdravlje, kliničke simptome, dijabetes i hematološke parametre. Izložena je skupina uspoređena s odgovarajućom kontrolnom skupinom od 187 ispitanika odgovarajuće dobi, spola i obrazovanja. Neurokognitivni poremećaj mjeren je s pomoću Inventara za subjektivnu procjenu neurokognitivne funkcije (izv. Subjective Neurocognition Inventory, krat. SNI), a mentalno zdravlje ocijenjeno s pomoću Upitnika o općem zdravstvenom stanju s 28 stavki (izv. General Health Questionnaire-28, krat. GHQ-28). Ispitanicima su također napravljene pretrage glukoze u krvi natašte (FBG), ureje u krvi (BUN), kolesterola (CL), triglicerida (TG), kreatinina, zatim test podnošljivosti oralne glukoze (GTT), lipoproteina visoke gustoće (HDL), aspartat aminotransferaze (AST), alanin aminotransferaze (ALT) i alkalne fosfataze (ALP). Izloženi zemljoradnici imali su značajno više nalaze FBG-a (p<0,001), BUN-a (p=0,007), CL-a (p<0,001) i GTT-a (p<0,001) te značajno niže nalaze AST-a (p<0,001), ALP-a (p<0,001) i kreatinina (p=0,004) od kontrolnih ispitanika. Također su u odnosu na kontrolu značajno češće imali tjeskobe/nesanice, odnosno snažnu depresiju (p=0,015, odnosno p<0,001). S druge strane, učestalost poremećaja socijalne funkcije bila je značajno manja nego u kontrolnih ispitanika (p<0,001). Svi poremećaji koji utječu na brzinu psihomotornog odgovora, selektivnu pažnju, podijeljenu pažnju, verbalno pamćenje, neverbalno pamćenje, prospektivno pamćenje, prostornu funkciju te inicijativu/energiju bili su slabije izraženi u zemljoradnika (p<0,001). Zemljoradnici su iskazali kliničke simptome poput ekcema, slinjenja, umora, glavobolje, znojenja, boli u trbuhu, mučnine, slabosti gornjih i donjih, distalnih i proksimalnih mišića te respiratornih mišića, trnaca u šakama i stopalima, epiforije, poliurije, mioze, dispneje, bradikardije i curenja iz nosa, a svi su simptomi bili značajno povezani s godinama staža. Ovi rezultati ispitivanja upućuju na to da su zemljoradnici koji rade s organofosfatima skloniji neuropsihološkim poremećajima i dijabetesu