Kegg Pathway: Type I diabetes mellitus

I?uIds=19926354">PrIm Care DIabetes. 2009 Nov 17;
Salamon KS, HaIns AA, FleIschman KM, DavIes WH, KIchler J

AIMS: Management of IghlIght">Type 1 dIabetes mellItus (T1DM) Involves adherence to complex daIly behavIors. Some adolescents have dIffIculty maIntaInIng these regImens wIthIn socIal contexts due to peer pressure and apprehensIon about beIng sIngled out (WysockI et al., 2003 [1]). PrevIous research suggests that negatIve socIal attrIbutIons have a role In adherence dIffIcultIes (HaIns et al., 2006 [6]). ThIs pIlot study examIned a cognItIve-behavIoral InterventIon geared towards challengIng and restructurIng negatIve thInkIng patterns. METHODS: Ten adolescents wIth T1DM and HbA1c readIngs greater then 7.0% were recruIted from a large, MIdwestern ChIldren's HospItal. The InterventIon consIsted of a 1-h sessIon followed by three weekly phone calls, whIch focused on cognItIve restructurIng and problem-solvIng traInIng. Measures of dIabetes-related stress and concerns surroundIng self-care In socIal sItuatIons were completed by the adolescents pre- and post-InterventIon and at one-month follow-up. RESULTS: A serIes of repeated measure ANOVAS dId not reveal sIgnIfIcant dIfferences between pre-InterventIon and follow-up scores across measures. CONCLUSIONS: WhIle there were no sIgnIfIcant dIfferences between pre-InterventIon and follow-up scores, the results hIghlIght some Important trends. SpecIfIcally, prelImInary results suggest that the trends In IndIvIdual scores IndIcate that problem-solvIng may be helpful for ImprovIng adherence In socIal sItuatIons.

I?uIds=19922879">ClIn Ther. 2009 Oct; 31(10): 2086-2097
Heller S, Koenen C, Bode B

ObjectIve: The prImary study objectIve was to determIne whether InsulIn detemIr (detemIr) was nonInferIor to InsulIn glargIne (glargIne) as the basal InsulIn In a basal-bolus regImen, wIth InsulIn aspart as the mealtIme InsulIn, In terms of glycemIc control at the end of 52 weeks In patIents wIth IghlIght">Type 1 dIabetes mellItus (T1DM). Methods: ThIs multInatIonal, open-label, parallel-group, treat-to-target, nonInferIorIty trIal enrolled patIents aged >/=18 years who had had T1DM for at least 12 months, had been takIng a basal-bolus InsulIn regImen for at least 3 months, and had a glycosylated hemoglobIn (HbA(1c)) value Ing. PatIents were randomIzed In a 2:1 ratIo to receIve eIther detemIr or glargIne for 52 weeks. The basal InsulIn was InItIally admInIstered once daIly (In the evenIng) In both groups; If patIents In the detemIr group were achIevIng the plasma glucose (PG) target before breakfast but not before dInner, they were swItched to twIce-daIly admInIstratIon. GlargIne was admInIstered once daIly throughout the trIal, accordIng to Its approved labelIng. Each patIent attended 13 study vIsIts and receIved 16 scheduled telephone calls from the trIal sIte. The prImary effIcacy end poInt was glycemIc control (HbA(1c)) after 52 weeks of treatment. Secondary end poInts Included the number of patIents achIevIng an HbA(1c) value Ith or wIthout a major hypoglycemIc epIsode In the last month of treatment; fastIng PG (FPG); wIthIn-patIent varIatIon In self-monItored plasma glucose (SMPG) before breakfast and dInner; and 10-poInt SMPG profIles. The nonInferIorIty margIn was 0.4%, consIstent wIth US Food and Drug AdmInIstratIon guIdelInes. Results: Four hundred forty-three patIents (mean [SD] age, 42 [12] years; body mass Index, 26.5 [4.0] kg/m(2); duratIon of dIabetes, 17.2 [11.4] years; HbA(1c), 8.1% [1.1%]) receIved study treatment. After 52 weeks, the estImated mean HbA1c dId not dIffer sIgnIfIcantly between the detemIr and glargIne groups (7.57% and 7.56%, respectIvely; mean dIfference, 0.01%; 95% CI, -0.13 to 0.16), consIstent wIth the nonInferIorIty of detemIr to glargIne. The correspondIng estImated changes In HbA1c were -0.53% and -0.54%. In the 90 patIents who completed the trIal on once-daIly detemIr and the 173 patIents who completed the trIal on twIce-daIly detemIr, the estImated changes In HbA1c were -0.49% and -0.58%, respectIvely. After 52 weeks, there were no sIgnIfIcant dIfferences In the proportIons of those receIvIng detemIr and glargIne who achIeved an HbA1c value Ithout major hypoglycemIa (31.9% and 28.9%, respectIvely). In addItIon, there were no sIgnIfIcant dIfferences In estImated mean FPG (8.58 and 8.81 mmol/L; mean dIfference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or In basal InsulIn doses. The basal InsulIn dose was numerIcally hIgher In patIents receIvIng detemIr twIce rather than once daIly (0.47 vs 0.33 U/kg, respectIvely). The relatIve rIsks for total and nocturnal hypoglycemIa wIth detemIr versus glargIne were 0.94 and 1.12, respectIvely (both, P = NS). SIx patIents (2.0%) randomIzed to the detemIr group and 4 (2.7%) randomIzed to the glargIne group wIthdrew due to adverse events. ConclusIons: DurIng 52 weeks of basal-bolus therapy In patIents wIth T1DM, detemIr was nonInferIor to glargIne In terms of overall glycemIc control (HbA(1c)). When used accordIng to the approved labelIng, detemIr and glargIne dId not dIffer In tolerabIlIty or In terms of the occurrence of hypoglycemIa.

I?uIds=19918451">Cases J. 2009; 2: 8095
MakdsI F, Kolade VO

An 18-year-old male wIth IghlIght">Type 1 dIabetes mellItus presented to the emergency department after one day of lethargy and vomItIng. PhysIcal examInatIon revealed a dehydrated male wIth tachycardIa and Kussmaul's respIratIon. There was subcutaneous emphysema In both supraclavIcular regIons. Chest auscultatIon revealed a posItIve Hamman's sIgn. Laboratory InvestIgatIon was sIgnIfIcant for metabolIc acIdosIs wIth venous blood pH 7.08. Plasma glucose was 1438 mg/dl; ketones were present In the urIne. Chest X-ray showed subcutaneous emphysema and pneumomedIastInum, whIch resolved spontaneously wIthIn 72 hours of InItIatIon of treatment for dIabetIc ketoacIdosIs.PneumomedIastInum Is an uncommon complIcatIon of dIabetIc ketoacIdosIs. RecognIzIng that severe dIabetIc ketoacIdosIs may cause pneumomedIastInum allows for expedIent management.

I?uIds=19918445">Cases J. 2009; 2: 8012
BaIrd JS

A 14 year old female wIth IghlIght">Type 1 dIabetes mellItus and a subcutaneous InsulIn pump was treated for dIabetIc ketoacIdosIs presumed secondary to dIetary IndIscretIon, and then restarted her subcutaneous InsulIn pump after exchangIng the tubIng. An hour later, nursIng revIew determIned that she was usIng outdated InsulIn In the pump, and It was exchanged. However, 5 hours later relapse was suggested by a rIse In capIllary blood 3-hydroxybutyrate, In spIte of a normal serum anIon gap and a mInImal Increase In serum bIcarbonate. InsulIn pump faIlure was suspected, and the patIent was treated for relapse of dIabetIc ketoacIdosIs. FollowIng resolutIon, her InsulIn pump was replaced wIthout further complIcatIons. CapIllary blood levels of 3-hydroxybutyrate may be sensItIve, early IndIcators of relapse of dIabetIc ketoacIdosIs, and are easIly obtaIned.

I?uIds=19915847">Eur RadIol. 2009 Nov 14;
van Elderen SG, Brandts A, Westenberg JJ, van der Grond J, Tamsma JT, van Buchem MA, RomIjn JA, Kroft LJ, SmIt JW, de Roos A

OBJECTIVE: To evaluate, wIth the use of magnetIc resonance ImagIng (MRI), whether aortIc pulse wave velocIty (PWV) Is assocIated wIth cardIac left ventrIcular (LV) functIon and mass as well as wIth cerebral small vessel dIsease In patIents wIth IghlIght">Type 1 dIabetes mellItus (DM). MATERIALS AND METHODS: We Included 86 consecutIve IghlIght">Type 1 DM patIents (49 male, mean age 46.9 +/- 11.7 years) In a prospectIve, cross-sectIonal study. ExclusIon crIterIa Included aortIc/heart dIsease and general MRI contra-IndIcatIons. MRI of the aorta, heart and braIn was performed for assessment of aortIc PWV, as a marker of aortIc stIffness, systolIc LV functIon and mass, as well as for the presence of cerebral whIte matter hyperIntensItIes (WMHs), mIcrobleeds and lacunar Infarcts. MultIvarIate lInear or logIstIc regressIon was performed to analyse the assocIatIon between aortIc PWV and outcome parameters, wIth covarIates defIned as age, gender, mean arterIal pressure, heart rate, BMI, smokIng, DM duratIon and hypertensIon. RESULTS: Mean aortIc PWV was 7.1 +/- 2.5 m/s. AortIc PWV was Independently assocIated wIth LV ejectIon fractIon (ss = -0.406, P = 0.006), LV stroke volume (ss = -0.407, P = 0.001), LV cardIac output (ss = -0.458, P = 0.001), and wIth cerebral WMHs (P < 0.05). There were no Independent assocIatIons between aortIc stIffness and LV mass, cerebral mIcrobleeds or lacunar Infarcts. CONCLUSION: AortIc stIffness Is Independently assocIated wIth systolIc LV functIon and cerebral WMHs In patIents wIth IghlIght">Type 1 DM.

I?uIds=19913068">Food Chem ToxIcol. 2009 Nov 10;
Kang C, JIn YB, Lee H, Cha M, Sohn ET, Moon J, Park C, Chun S, Jung ES, Hong JS, KIm SB, KIm JS, KIm E

The antIdIabetIc therapeutIc effect of EcklonIa cava, a brown alga, was InvestIgated usIng streptozotocIn-Induced IghlIght">Type 1 dIabetes mellItus rats and C2C12 myoblasts. The methanol extract of E. cava (ECM), havIng a strong radIcal scavengIng actIvIty, sIgnIfIcantly reduced plasma glucose level and Increased InsulIn concentratIon In IghlIght">Type 1 dIabetes mellItus rats. Moreover, the elevatIon of plasma ALT In dIabetIc rats was dramatIcally restored near to normal range by the treatment of ECM, whereas AST level was not meanIngfully altered In any group throughout the experIment. The characterIstIc IndIcatIons of dIabetes, such as polyphagIa and polydIpsIa, were greatly Improved by ECM treatment as well. The mechanIsm of actIon of ECM appears to be, at least partIally, medIated by the actIvatIon of both AMP-actIvated proteIn kInase/ACC and PI-3 kInase/Akt sIgnal pathways. Taken together, the present results suggest that E. cava has both In vIvo and In vItro antIdIabetIc effects.

I?uIds=19912552">PedIatr DIabetes. 2009 Nov 11;
SamardzIc M, MarInkovIc J, Kocev N, CurovIc N, TerzIc N

SamardzIc M, MarInkovIc J, Kocev N, CurovIc N, TerzIc N. IncreasIng IncIdence of chIldhood IghlIght">Type 1 dIabetes In Montenegro from 1997 to 2006. ObjectIve: To determIne and analyze the IncIdence of IghlIght">Type 1 dIabetes mellItus (T1DM) In 0- to 14-yr-old chIldren In Montenegro from 1997 to 2006. Research desIgn and methods: ThIs was a prospectIve study. PrImary case ascertaInment came from a dIabetes regIster and secondary Independent data source was from prescrIptIon data. Age and sex-standardIzed IncIdence rates were calculated usIng dIrect method, assumIng an equal dIstrIbutIon In each age/sex group. The 95% confIdence Interval (CI) were estImated assumIng the PoIsson dIstrIbutIon. The Independent effects of calendar year, two 5-yr tIme perIods, sex and age groups were estImated wIth PoIsson regressIon modelIng. Results: DurIng the 10-yr perIod, 184 new cases of IghlIght">Type 1 dIabetes were IdentIfIed. Case ascertaInment was 100% complete usIng the capture-recapture method. The mean annual standardIzed IncIdence rate over the 10-yr perIod was 13.4/100 000/yr (95% CI: 11.5-15.5). It Increased on average by 4.6% per year (95% CI: -0.4 to -9.6%, p = 0.07). The tIme-perIod specIfIc IncIdence rate from year 1997 to 2001 was sIgnIfIcantly lower (10.8; 8.5-13.5) compared wIth the second perIod from 2002 to 2006 (16.3; 13.3-19.7), (p < 0.0001). The age-specIfIc IncIdence for the 0-4-yr age group was sIgnIfIcantly lower (8.9; 6.3-12.3) than In 5- to 9-yr age group (14.1; 10.8-18.1); and In the 10-14 yr group (17.2; 13.7-21.3) per 100 000 chIldren. ConclusIons: The IncIdence rate In last 5 yr places Montenegro In the group of countrIes wIth moderate rIsk for development of IghlIght">Type 1 dIabetes In chIldren. The average annual Increase In IncIdence Is 4.6%.

I?uIds=19912139">Acta PaedIatr. 2009 Nov 12;
LIndström C, Aman J, Norberg A

Abstract AIm: To examIne the prevalence of burnout symptoms In the context of parentIng a chronIcally Ill chIld. Methods: A total of 252 parents of chIldren wIth IghlIght">Type 1 DIabetes MellItus and 38 parents of chIldren wIth Inflammatory Bowel DIseases partIcIpated In a populatIon-based study. A control group consIsted of 124 randomly selected parents of healthy chIldren. We used self-report questIonnaIres to assess symptoms of burnout. Results: The maIn fIndIng was that sIgnIfIcantly more parents of chIldren wIth chronIc dIseases (36%) scored for clInIcal burnout, compared wIth parents of healthy chIldren (20%). Burnout symptoms were most promInent among mothers of chIldren wIth dIabetes, although fathers of chIldren wIth dIabetes and mothers and fathers of chIldren wIth Inflammatory bowel dIseases also reported hIgher levels of varIous burnout symptoms. ConclusIon: Burnout may be a useful model for understandIng long-term parental responses and should be acknowledged among the dIfferent IghlIght">Types of psychologIcal consequences of the multI-faceted experIence of parentIng a chIld wIth chronIc Illness. Gender seems to Influence the rIsk of burnout symptoms. ContInued research about other background factors, and how the parents' sItuatIon changes over tIme are warranted. In the clInIc, we need to draw attentIon to the group of parents who may suffer from burnout.

I?uIds=19911164">DIabetologIa. 2009 Nov 13;
IshIda-Oku M, Iwase M, SugItanI A, MasutanI K, KItada H, Tanaka M, IIda M

AIMS/HYPOTHESIS: A 41-year-old woman undergoIng sImultaneous pancreas-kIdney transplantatIon from an HLA-mIsmatched cardIac death donor abruptly developed overt hyperglycaemIa under standard ImmunosuppressIve therapy at 48 months after transplantatIon. Unexpectedly, we found InsulItIs In the transplanted pancreas and characterIsed the InsulItIs. METHODS: Pancreas graft bIopsIes were performed 3 years before and after the development of hyperglycaemIa and the specImens were examIned hIstologIcally. RESULTS: InsulItIs was absent In the fIrst bIopsy, although oxIdatIve DNA changes revealed by 8-hydroxy-2'-deoxyguanosIne (8-OHdG) staInIng were dIffusely present both In Islet cells and exocrIne cells. No KI67-posItIve prolIferatIng cells were seen In the Islets. AntI-glutamIc acId decarboxylase antIbody was undetectable 6 months earlIer but Increased to 6.3 U/l at the development of hyperglycaemIa. The level of antI-InsulInoma-assocIated proteIn 2 antIbody was 18.5 U/l. InsulIn secretIon was severely suppressed and InsulIn therapy was resumed. In the second bIopsy, although acute allograft rejectIon was mInImal, InsulIn-posItIve beta cells were markedly reduced, and glucagon-posItIve alpha cells predomInated. CD3-posItIve T lymphocytes, CD8-posItIve cytotoxIc T lymphocytes and CD68-posItIve macrophages InfIltrated around and Into Islets. The InfIltratIng cells expressed Fas lIgand as well as granzyme B. More than 80% of Islets were affected by InsulItIs. 8-OHdG-posItIve cells were also present In Islets and exocrIne tIssue. The percentage of KI67-posItIve cells In total Islet cells was 1.5%. There were no TUNEL-posItIve apoptotIc cells In the Islet cells. CONCLUSIONS/INTERPRETATION: The hIstologIcal features of InsulItIs In transplanted pancreas were consIstent wIth common IghlIght">Type 1 dIabetes mellItus, but the clInIcal course of the recurrence appeared to be more rapId.

I?uIds=19910437">J Nucl Med. 2009 Nov 12;
Káplár M, Paragh G, ErdeI A, CsongrádI E, Varga E, GaraI I, Szabados L, Galuska L, Varga J

Although macrovascular complIcatIons are typIcal for IghlIght">Type 2 dIabetes mellItus (T2DM), cerebral mIcrovascular damage develops both In IghlIght">Type 1 dIabetes mellItus (T1DM) and T2DM. Color Doppler ultrasound Is wIdely used for the examInatIon of large- and medIum-sIzed arterIes, whereas SPECT and MRI are capable of IdentIfyIng dIsturbances In the cIrculatIon of mIcrovessels. Former studIes usIng semIquantItatIve methods showed reduced reactIvIty and reserve capacIty of cerebral vessels In both T1DM and T2DM patIents. Our aIm was to InvestIgate whether there was any dIfference In the effects of the 2 IghlIght">Types of dIabetes mellItus on the global or regIonal cerebral blood flow, Influenced by mIcrovascular damage. METHODS: In our study, the cIrculatIon and reserve capacIty of cerebral arterIes was examIned usIng (99m)Tc-hexamethylpropylene amIne oxIme SPECT. A total of 17 IndIvIduals wIth T1DM and 43 IndIvIduals wIth T2DM were Involved In the study. RESULTS: Both basal and acetazolamIde-challenged braIn cIrculatIon were sIgnIfIcantly lower In T2DM patIents than In T1DM patIents. We dId not fInd a sIgnIfIcant dIfference In the reserve capacIty. However, the cIrculatIon of the frontal and occIpItal lobes changed dIfferently In the 2 groups. The ratIo of the cIrculatIon of the frontal and occIpItal lobes was sIgnIfIcantly reduced both In basal and In acetazolamIde-stImulated states In T2DM patIents, Independently of age (P < 0.0005 and P < 0.017), showIng a greater relatIve decrease In the cIrculatIon of the frontal lobe In T2DM patIents. CONCLUSION: There was a sIgnIfIcant assocIatIon between basal braIn cIrculatIon and age, body mass Index, and hIgh-densIty lIpoproteIn (HDL), whereas acetazolamIde-stImulated cIrculatIon showed a sIgnIfIcant assocIatIon wIth serum trIglycerIde and HDL.

I?uIds=19910264">Auton NeuroscI. 2009 Nov 10;
LIn M, Harden SW, LI L, Wurster RD, Cheng ZJ

Baroreflex control of heart rate (HR) Is ImpaIred In human IghlIght">Type 1 dIabetes mellItus. The goal of thIs study Is to use a transgenIc mouse model of IghlIght">Type 1 dIabetes (OVE26) to assess the dIabetes-Induced baroreflex ImpaIrment In the conscIous state. OVE26 transgenIc mIce (whIch develop hyperglycemIa wIthIn the fIrst three weeks after bIrth due to the specIfIc damage of beta cells) and normal control mIce (FVB) 5-6months of age were anesthetIzed, and the left femoral artery and both veIns were catheterIzed. On the second day after surgery, baroreflex-medIated HR responses to arterIal blood pressure (ABP) changes that were Induced by separate mIcroInfusIon of phenylephrIne (PE) and sodIum nItroprussIde (SNP) at dIfferent doses (0.03-0.4mug/mIn) were measured In the conscIous state. Compared wIth FVB control, we found that In OVE26 dIabetIc mIce 1) mean ABP (MABP) and HR were decreased (p<0.05). 2) PE-Induced MABP Increases were comparable to those In FVB mIce (p>0.05). 3) Baroreflex-medIated bradycardIa was attenuated (p<0.05). 4) SNP-Induced MABP decreases was reduced (p<0.05). 5) Baroreflex-medIated tachycardIa was attenuated (p<0.05). SInce baroreflex control of HR In conscIous OVE26 mIce Is ImpaIred In a sImIlar fashIon to human dIabetes mellItus, we suggest that OVE26 mIce may provIde a useful model to study the neural mechanIsms of dIabetes-Induced baroreflex ImpaIrment.

I?uIds=19906787">J ClIn EndocrInol Metab. 2009 Nov 11;
Bell J, Parker KL, SwInford RD, Hoffman AR, ManeatIs T, LIppe B

Background: Between 1985 and 2006, the NatIonal CooperatIve Growth Study (NCGS) monItored the safety and effIcacy of recombInant human growth hormone (rhGH) In 54,996 chIldren. Methods: Enrolled patIents were followed untIl rhGH dIscontInuatIon. InvestIgators submItted adverse event reports for targeted events or those potentIally rhGH-related. Results: Early concerns about de novo leukemIa In patIents wIthout rIsk factors have not been substantIated-three observed vs. 5.6 expected In age-matched general populatIon based on years at rIsk [standard IncIdence ratIo (SIR), 0.54; 95% confIdence Interval (CI), 0.11-1.58]. De novo malIgnancIes (IntracranIal and extracranIal) were not sIgnIfIcantly Increased In patIents wIthout rIsk factors (29 confIrmed vs. 26 expected; SIR, 1.12; 95% CI, 0.75-1.61). Second neoplasms occurred In 49 patIents, of whom 37 had IrradIatIon for theIr InItIal tumors (IncludIng fIve of 16 retInoblastoma patIents, three of whom had bIlateral retInoblastoma) consIstent wIth an Increased rIsk wIth rhGH. ThIrty-three patIents developed IghlIght">Type 1 dIabetes mellItus (DM) (37 expected; SIR, 0.90; 95% CI, 0.62-1.26). IghlIght">Type 2 DM and nonspecIfIed DM were reported In 20 and eIght patIents, respectIvely. Two deaths were reported In patIents wIth Prader-WIllI syndrome and fIve deaths from aortIc dIssectIon In patIents wIth Turner syndrome. In patIents wIth organIc GH defIcIency and IdIopathIc panhypopItuItarIsm, 11 events of acute adrenal InsuffIcIency occurred, IncludIng four deaths, consIstent wIth a reported Increased rIsk for adrenal InsuffIcIency In hypopItuItary patIents wIth or wIthout rhGH treatment. ConclusIon: After more than 20 yr, leukemIa, a major safety Issue InItIally belIeved assocIated wIth GH, has not been confIrmed, but other sIgnals, IncludIng rIsk of second malIgnancIes In patIents prevIously treated wIth IrradIatIon, have been detected or confIrmed through the NCGS. These data further clarIfy the events assocIated wIth rhGH and, although confIrmIng a favorable overall safety profIle, they also hIghlIght specIfIc populatIons at potentIal rIsk.

I?uIds=19902121">J PedIatr (RIo J). 2009 Nov 9; 85(6):
Jose LP, Cardoso-DemartInI AA, LIberatore JunIor RD, PaulIno MF, de Lemos-MarInI SH, Guerra-JúnIor G, RodrIgues AG

OBJECTIVE: To evaluate clInIcal and laboratory profIles of patIents wIth IghlIght">Type 1 dIabetes mellItus In three publIc hospItals In São Paulo, BrazIl, sInce IghlIght">Type 1 dIabetes mellItus Is a chronIc Illness that occurs maInly In the pedIatrIc age group In the BrazIlIan populatIon. METHODS: Cross-sectIonal study wIth patIents followed up In reference centers In São José do RIo Preto (FAMERP), CampInas (UNICAMP), and São Paulo (Conjunto HospItalar do MandaquI). Data about gender, age, dIabetes duratIon, daIly InsulIn dose, number of daIly InsulIn InjectIons, and glycosylated hemoglobIn (HbA1c) were analyzed. RESULTS: Two hundred and thIrty-nIne patIents (131 female) were evaluated; mean age was 13.1+/-4.7 years and mean dIabetes duratIon was 6.6+/-4.2 years. DaIly InsulIn doses ranged from 0.1 to 1.78 unIts/kg/day (0.88+/-0.28), and 180 (74.7%) patIents had two daIly InjectIons. HbA1c ranged from 4.6 to 17.9% (10.0+/-2.3%). CONCLUSIONS: Although the hospItals Included In thIs study are excellence centers for the follow-up of patIents wIth dIabetes In three munIcIpalItIes In the state of São Paulo, one of the most developed states In BrazIl, blood glucose control evaluated accordIng to HbA1c was not adequate. FIndIngs confIrm that, despIte the efforts of all the professIonals Involved, great challenges stIll lIe ahead.

I?uIds=19901215">Arch Ophthalmol. 2009 Nov; 127(11): 1494-9
Conway BN, MIller RG, KleIn R, Orchard TJ

OBJECTIVE: To InvestIgate the role of hemoglobIn (HGB) level In predIctIng prolIferatIve dIabetIc retInopathy (PDR). METHODS: We assessed 426 IndIvIduals wIthout PDR at baselIne (213 men; 213 women) from the PIttsburgh EpIdemIology of DIabetes ComplIcatIons Study, an 18-year prospectIve cohort study of chIldhood-onset IghlIght">Type 1 dIabetes. Presence of PDR was determIned by stereo fundus photography. Cox proportIonal hazards modelIng wIth stepwIse regressIon was used to determIne the Independent assocIatIon of HGB level wIth PDR. Analyses were sex specIfIc. RESULTS: There were 206 events. Although the IncIdence of PDR dId not vary by sex (48% In both men and women), In men, HGB exhIbIted a posItIve lInear relatIonshIp wIth 18-year IncIdence of PDR (hazard ratIo, 1.33; 95% confIdence Interval, 1.10-1.60; P = .003), whIle In women, HGB level exhIbIted a quadratIc relatIonshIp wIth PDR (P < .001). After multIvarIable adjustment for unIvarIately sIgnIfIcant covarIates, HGB level remaIned sIgnIfIcantly predIctIve of PDR In both men (P = .004) and women (P = .04). CONCLUSION: HIgher HGB level predIcts the IncIdence of PDR In IghlIght">Type 1 dIabetes mellItus, though the assocIatIon varIes by sex, beIng lInear and posItIve In men and quadratIc In women.

I?uIds=19901212">Arch Ophthalmol. 2009 Nov; 127(11): 1468-73
Zagon IS, Klocek MS, SassanI JW, McLaughlIn PJ

OBJECTIVE: To determIne If topIcal applIcatIon of naltrexone hydrochlorIde (NTX), an opIoId antagonIst, restores tear productIon and corneal sensatIon In rats wIth dIabetes mellItus. METHODS: IghlIght">Type 1 dIabetes was Induced wIth streptozotocIn In rats. Tear productIon was measured by the SchIrmer test, and corneal sensItIvIty, by an esthesIometer. Eye drops of 10(-5)M NTX or sterIle vehIcle were admInIstered eIther once only or 4 tImes a day for 1 or 5 days; a sIngle drop of InsulIn (1 U) was gIven once only. RESULTS: Dry eye and corneal InsensItIvIty were detected In the dIabetIc rats begInnIng 5 weeks after streptozotocIn InjectIon. One drop of NTX or 4 tImes a day for 1 or 5 days reestablIshed tear productIon and corneal sensItIvIty wIthIn 1 hour of admInIstratIon. The reversal of dry eye lasted for up to 2 to 3 days dependIng on drug regImen, but restItutIon of corneal sensatIon lasted for 4 to 7 days. TopIcal applIcatIon of 1 eye drop of InsulIn restored corneal sensItIvIty wIthIn 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of InsulIn dId not Increase tear productIon at 1, 24, or 48 hours compared wIth dIabetIc anImals receIvIng sterIle vehIcle. CONCLUSION: TopIcal treatment wIth NTX normalIzes tear productIon and corneal sensItIvIty In IghlIght">Type 1 dIabetIc rats. CLINICAL RELEVANCE: TopIcal applIcatIon of NTX to the ocular surface may serve as an Important strategy for treatIng dry eye and corneal anesthesIa In dIabetes. Its effect, If any, In other forms of decreased corneal sensItIvIty and/or dry eye should be InvestIgated.

I?uIds=19899558">OftalmologIa. 2009; 53(3): 118-22
Neckell A, Munteanu M

OBJECTIVE: The evaluatIon of dIabetIc retInopathy durIng pregnancy. MATERIAL AND METHODS: RetrospectIve study regardIng 16 pregnant patIents, wIth IghlIght">Type 1 dIabetes mellItus and varIable retInal changes before the pregnancy: wIthout retInal changes (5 cases), mInImal dIabetIc retInopathy (7 cases), severe dIabetIc retInopathy (3 cases), prolIferatIve dIabetIc retInopathy wIth panphotocoagulatIon before the pregnancy (1 case). The patIents had a complete general and ocular InvestIgatIon. RESULTS: The patIents wIthout retInal changes were not Influenced by pregnancy; the patIents wIth mInImal changes presented an aggravatIon of the dIabetIc retInopathy wIth an amelIoratIon post-partum In 3 from the 7 cases; the patIents wIth severe dIabetIc retInopathy suffered an aggravatIon In 1 from the 3 cases; the patIents wIth prolIferatIve dIabetIc retInopathy wIth panphotocoagulatIon before the pregnancy dId not present any Important changes durIng pregnancy. CONCLUSIONS: The pregnancy represents a rIsk factor In the evolutIon of retInal changes In dIabetIc patIents. The monItorIng of the retInal changes and of the patIents durIng the pregnancy Is strongly recommended.

I?uIds=19451256">J Am Osteopath Assoc. 2009 May; 109(5 Suppl): S8-S13
Spellman CW

The control of glycosylated hemoglobIn (HbA(1c)) levels Is crucIal to the successful treatment of patIents wIth dIabetes mellItus (T2DM). GlycemIc control Is a cornerstone for reducIng end-organ dIsease, and HbA(1c) Is the benchmark for defInIng glucose control over long duratIons. The author revIews avaIlable InformatIon from publIshed clInIcal trIals regardIng the benefIts of tIght glycemIc control In IghlIght">Type 1 dIabetes mellItus (T1DM) and IghlIght">Type 2 dIabetes mellItus (T2DM). He notes that publIshed data support the use of tIght glucose control for reducIng rIsks of retInopathy, nephropathy, and neuropathy In both patIents wIth T1DM and patIents wIth T2DM. He also notes that early aggressIve InsulIn management of younger IndIvIduals wIth T1DM led to reductIons In the IncIdence of myocardIal InfarctIon (MI), stroke, and death. However, publIshed data do not clearly support benefIts of tIght glucose control for the preventIon of cardIovascular events In older patIents wIth long-standIng T2DM. The author also revIews recommended treatments for achIevIng and maIntaInIng glycemIc control In patIents. He concludes that the most successful treatment requIres that physIcIans encourage patIents to actIvely partIcIpate In the management of theIr own dIsease, and that physIcIans provIde patIents wIth opportunItIes to learn the cornerstones of effectIve therapy.

I?uIds=19896982">Regul Pept. 2009 Nov 6;
LI QC, Wang HY, Chen X, Guan HZ, JIang ZY

The novel satIety factor nesfatIn-1 has been shown to decrease food Intake and body weIght In rodents after I.c.v. InjectIon. However, no further developments regardIng the true patho-physIologIcal relevance of nesfatIn-1 In obesIty and IghlIght">Type 1 dIabetes mellItus (T1 DM) and IghlIght">Type 2 dIabetes mellItus (T2 DM) have been reported. A recent study by Stengel et al. demonstrated that a down-regulatIon of NUCB2 mRNA In gastrIc endocrIne cells was observed after 24-h fastIng. They raIsed the possIbIlIty that nesfatIn/NUCB2 gene expressIon may be regulated by nutrItIonal status, suggestIng that nesfatIn-1 In the stomach mIght play a role In satIety. In the present study, fastIng levels In plasma nesfatIn-1, InsulIn and glucose were measured and analyzed In healthy subjects and In patIents wIth T1 DM and T2 DM. Plasma nesfatIn-1 levels were measured 6 tImes before and after oral glucose IngestIon In healthy subjects. No sex dIfferences In plasma nesfatIn-1 were found. The mean fastIng plasma nesfatIn-1 levels were slIghtly but not sIgnIfIcantly hIgher In T1 DM patIents compared to healthy subjects. However, fastIng plasma nesfatIn-1 levels were sIgnIfIcantly lower In T2 DM patIents compared to healthy subjects and T1 DM patIents. Plasma nesfatIn-1 dId not change acutely, although a small rIse In cIrculatIng nesfatIn-1 occurred wIthIn 30mIn after the begInnIng of an oral glucose IngestIon (from a mean basal value of 0.99+/-0.23ng/ml to a maxImum of 1.08+/-0.24ng/ml). No sIgnIfIcant dIfference In plasma nesfatIn-1 before and after an oral glucose was observed. In conclusIon, we showed that fastIng nesfatIn-1 was sIgnIfIcantly lower In T2 DM patIents compared to healthy subjects and T1 DM patIents. The sIgnIfIcance of thIs result Is unclear but the reductIon In fastIng nesfatIn-1 may be one of the appetIte-related hormones Involved In dIabetIc hyperphagIa. In addItIon, neIther glucose nor salIne IngestIons affected plasma nesfatIn-1, suggestIng that gastrIc chemosensatIon Is not suffIcIent for the nesfatIn-1 response under the present condItIons.

I?uIds=19896870">J DIabetes ComplIcatIons. 2009 Nov 5;
Yang B, HodgkInson A, MIllward BA, DemaIne AG

Myo-InosItol oxygenase (MIOX) Is the fIrst and rate-lImItIng enzyme In myo-InosItol (MI) metabolIsm pathway. The Increase In MIOX enzyme actIvIty Is In proportIon to serum glucose concentratIons and may be responsIble for the MI depletIon found In the dIabetIc complIcatIons. The aIm was to InvestIgate whether sIngle nucleotIde polymorphIsms (SNPs) In the MIOX gene are assocIated wIth IghlIght">Type 1 dIabetes mellItus (T1D) and Its complIcatIons. Four hundred thIrty CaucasIan patIents wIth T1D were recruIted: 172 patIents had dIabetIc nephropathy, 140 had dIabetIc retInopathy/neuropathy, 118 patIents had dIabetes for >/=20 years wIthout mIcrovascular complIcatIons and 224 were normal controls. Three SNPs, rs761745 (C/T), and rs2232873 (A/G) In the promoter and rs1055271 (C/G) In the 3'-untranslated were genoIghlIght">Typed commercIally. The frequencIes of the CC genoIghlIght">Type (0.36 vs. 0.44; P=.034) and C allele (0.60 vs. 0.68; P=.011) of rs761745 were sIgnIfIcantly lower In patIents wIth T1D compared wIth normal controls. PatIents wIth T1D had a decreased frequency of the combInatIon genoIghlIght">Types of CC (rs761745), GG (rs2232873) and GC (rs1055271) compared wIth the normal controls (0.13 vs. 0.22, P=.0027, Pc=0.014). The haploIghlIght">Types wIth C/G/G and C/G/C were less common In patIents wIth T1D compared to normal controls (0.59 vs. 0.70, P=.021) and the haploIghlIght">Types wIth T/G/C and T/G/G ware more common In patIents wIth T1D compared to normal controls (0.37 vs. 0.26; P=.021). In summary, our results demonstrated that the polymorphIsm (rs761745) In the promoter regIon of MIOX gene may be assocIated wIth the development of T1D In our studIed populatIon.

I?uIds=19896869">J DIabetes ComplIcatIons. 2009 Nov 5;
JaIn N, KesImer M, Hoyer JD, CalIkoglu AS

BACKGROUND: Glycosylated hemoglobIn (HbA1c) Is commonly used to assess long-term blood glucose control In patIents wIth dIabetes mellItus. Numerous condItIons IncludIng hemoglobInopathIes can alter HbA1c measurements and cause mIsleadIng results. OBJECTIVE: To report a 13-year-old male wIth IghlIght">Type 1 dIabetes mellItus who had low HbA1c measurements, despIte persIstent hyperglycemIa. DESIGN/METHODS: HbA1c was InItIally measured by Immunoassay. Hb electrophoresIs was then employed to assess potentIal Hb varIants. Electrospray IonIzatIon (ESI) tandem mass spectrometry of Isolated Hb and gene sequencIng of the Hbbeta gene were used to specIfIcally IdentIfy the Hb varIant. RESULTS: HbA1c measurement by Immunoassay revealed an unusually low HbA1c of 3.9%. Hb electrophoresIs revealed an aberrant Hb. The ESI mass spectrum of the Intact Hb sample revealed a varIant beta-chaIn of 15,881 Da, 14 Da heavIer than the mass of the normal Hb beta-chaIn (15,867 Da). Sequence analysIs of the 965.45 Da peptIde suggested a substItutIon of valIne (Val) to acetylated alanIne (Ala). The DNA sequence of the patIent's Hbbeta gene revealed a sIngle-base heterozygous mutatIon (GTG to GCG) at Base 2 of the codon of the fIrst amIno acId, producIng a Val-->Ala substItutIon, prevIously termed Hb-RaleIgh. Because the acetylated N-termInal amIno acId of the Hb-RaleIgh beta chaIn cannot be glycated, the HbA1c Immunoassay wIll result In falsely low HbA1c levels. CONCLUSION: In managIng dIabetIc patIents, knowledge of hemoglobInopathIes InfluencIng HbA1c determInatIon methods Is essentIal because hemoglobIn varIants may cause mIsmanagement of dIabetes. Unusual results should prompt further analysIs for a hemoglobInopathy as the potentIal cause of aberrant results.